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image of Melittin Inhibits Ovarian Cancer Cell Growth by Downregulating MMP9 Expression via the JAK2-STAT3 Signaling Pathway

Abstract

Objective

This study aimed to investigate the target sites, core pathways, and mechanisms of action of melittin in treating ovarian cancer through network pharmacology, molecular docking, and experimental verification.

Methods

Potential targets for melittin in ovarian cancer treatment were predicted using databases, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. The binding of the drug to these targets was confirmed through molecular docking. The core targets and pathways were experimentally validated. A tumor-bearing nude mouse model was established, with the mice randomly divided into treatment and control groups. The treatment group received 5 mg/kg of melittin by intraperitoneal injection, whereas the control group received saline injections. Changes in mouse weight and tumor volume were monitored, and protein expression in mouse tumor tissues was assessed immunohistochemistry and Western blotting at the end of the experiment.

Results

Fifty-three common targets between melittin and ovarian cancer were identified in the SEA and GeneCards databases. The Protein-Protein Interaction (PPI) analysis highlighted core targets, including MMP9, STAT3, MMP2, STAT6, FURIN, and BRCA1. The GO enrichment results were related mainly to the metabolic processes of collagen degradation, extracellular matrix disassembly, external encapsulating structures, and phospholipase C-activated G-protein-coupled receptor signaling pathways. The KEGG pathway analysis revealed the enrichment of genes related to estrogen signaling, necroptotic apoptosis, the FoxO signaling pathway, microRNAs in cancer, the JAK-STAT signaling pathway, proteoglycans in cancer, and receptor-mediated carcinogenesis. Cell Counting Kit-8 (CCK8) assays, scratch wound healing tests, and Transwell invasion assays demonstrated that melittin significantly inhibited the proliferation, migration, and invasion of ovarian cancer cells. The Western blot results indicated that melittin downregulated the levels of p-JAK2, p-STAT3, and MMP9 in ovarian cancer cells. Molecular docking demonstrated that melittin bound stably to MMP9 and STAT3. The results of animal experiments indicated that melittin suppressed the growth of ovarian tumors in nude mice and significantly downregulated the expression of MMP9, p-JAK2, and p-STAT3 in tumor tissues (<0.05).

Conclusion

Melittin may inhibit the growth of ovarian cancer cells by downregulating MMP9 expression the JAK2-STAT3 signaling pathway, thus exerting a therapeutic effect.

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2025-04-29
2025-09-11

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References

  1. Siegel R.L. Miller K.D. Wagle N.S. Jemal A. Cancer statistics, 2023. CA Cancer J. Clin. 2023 73 1 17 48 10.3322/caac.21763 36633525
    [Google Scholar]
  2. Webb P.M. Jordan S.J. Global epidemiology of epithelial ovarian cancer. Nat. Rev. Clin. Oncol. 2024 21 5 389 400 10.1038/s41571‑024‑00881‑3 38548868
    [Google Scholar]
  3. McCluggage W.G. Singh N. Gilks C.B. Key changes to the World Health Organization (WHO) classification of female genital tumours introduced in the 5th edition (2020). Histopathology 2022 80 5 762 778 10.1111/his.14609
    [Google Scholar]
  4. Lliberos C. Richardson G. Papa A. Oncogenic pathways and targeted therapies in ovarian cancer. Biomolecules 2024 14 5 585 10.3390/biom14050585 38785992
    [Google Scholar]
  5. Yang L. Xie H.J. Li Y.Y. Wang X. Liu X.X. Mai J. Molecular mechanisms of platinum-based chemotherapy resistance in ovarian cancer (Review). Oncol. Rep. 2022 47 4 82 10.3892/or.2022.8293 35211759
    [Google Scholar]
  6. Havasi A. Cainap S.S. Havasi A.T. Cainap C. Ovarian cancer—insights into platinum resistance and overcoming it. Medicina 2023 59 3 544 10.3390/medicina59030544 36984544
    [Google Scholar]
  7. Wang K. Chen Q. Shao Y. Yin S. Liu C. Liu Y. Wang R. Wang T. Qiu Y. Yu H. Anticancer activities of TCM and their active components against tumor metastasis. Biomed. Pharmacother. 2021 133 111044 10.1016/j.biopha.2020.111044 33378952
    [Google Scholar]
  8. Yang Y. Shen J. Deng P. Chen P. Mechanism investigation of Forsythoside A against esophageal squamous cell carcinoma in vitro and in vivo. Cancer Biol. Ther. 2024 25 1 2380023 10.1080/15384047.2024.2380023 39046082
    [Google Scholar]
  9. Wang Y. Guan W.X. Zhou Y. Zhang X.Y. Zhao H.J. Red ginseng polysaccharide promotes ferroptosis in gastric cancer cells by inhibiting PI3K/Akt pathway through down-regulation of AQP3. Cancer Biol. Ther. 2024 25 1 2284849 10.1080/15384047.2023.2284849 38051132
    [Google Scholar]
  10. Naeem A. Hu P. Yang M. Zhang J. Liu Y. Zhu W. Zheng Q. Natural products as anticancer agents: Current status and future perspectives. Molecules 2022 27 23 8367 10.3390/molecules27238367 36500466
    [Google Scholar]
  11. Wang K. Cai M. Sun S. Cheng W. Zhai D. Ni Z. Yu C. Therapeutic prospects of polysaccharides for ovarian cancer. Front. Nutr. 2022 9 879111 10.3389/fnut.2022.879111 35464007
    [Google Scholar]
  12. Muhammad N. Usmani D. Tarique M. Naz H. Ashraf M. Raliya R. Tabrez S. Zughaibi T.A. Alsaieedi A. Hakeem I.J. Suhail M. The role of natural products and their multitargeted approach to treat solid cancer. Cells 2022 11 14 2209 10.3390/cells11142209
    [Google Scholar]
  13. Liu K. Li Q. Lu X. Fan X. Yang Y. Xie W. Kang J. Sun S. Zhao J. Seven oral traditional Chinese medicine combined with chemotherapy for the treatment of non-small cell lung cancer: A network meta-analysis. Pharm. Biol. 2024 62 1 404 422 10.1080/13880209.2024.2351940 38739082
    [Google Scholar]
  14. Ramirez L.S. Pande J. Shekhtman A. Helical structure of recombinant melittin. J. Phys. Chem. B 2019 123 2 356 368 10.1021/acs.jpcb.8b08424 30570258
    [Google Scholar]
  15. Wimley W.C. How does melittin permeabilize membranes? Biophys. J. 2018 114 2 251 253 10.1016/j.bpj.2017.11.3738 29401422
    [Google Scholar]
  16. Badr-Eldin S.M. Alhakamy N.A. Fahmy U.A. Ahmed O.A.A. Asfour H.Z. Althagafi A.A. Aldawsari H.M. Rizg W.Y. Mahdi W.A. Alghaith A.F. Alshehri S. Caraci F. Caruso G. Cytotoxic and pro-apoptotic effects of a sub-toxic concentration of Fluvastatin on OVCAR3 ovarian cancer cells after its optimized formulation to melittin nano-conjugates. Front. Pharmacol. 2021 11 642171 10.3389/fphar.2020.642171 33633571
    [Google Scholar]
  17. Gajski G. Leonova E. Sjakste N. Bee venom: Composition and anticancer properties. Toxins 2024 16 3 117 10.3390/toxins16030117 38535786
    [Google Scholar]
  18. Wang K. Tao L. Zhu M. Yu X. Lu Y. Yuan B. Hu F. Melittin inhibits colorectal cancer growth and metastasis by activating the mitochondrial apoptotic pathway and suppressing epithelial–mesenchymal transition and angiogenesis. Int. J. Mol. Sci. 2024 25 21 11686 10.3390/ijms252111686 39519238
    [Google Scholar]
  19. Pandey P. Khan F. Khan M.A. Kumar R. Upadhyay T.K. An updated review summarizing the anticancer efficacy of melittin from bee venom in several models of human cancers. Nutrients 2023 15 14 3111 10.3390/nu15143111 37513529
    [Google Scholar]
  20. Wang X. Xie J. Lu X. Li H. Wen C. Huo Z. Xie J. Shi M. Tang X. Chen H. Peng C. Fang Y. Deng X. Shen B. Melittin inhibits tumor growth and decreases resistance to gemcitabine by downregulating cholesterol pathway gene CLU in pancreatic ductal adenocarcinoma. Cancer Lett. 2017 399 1 9 10.1016/j.canlet.2017.04.012 28428074
    [Google Scholar]
  21. Luo Y. Xu C. Luo B. Liang G. Zhang Q. Melittin treatment prevents colorectal cancer from progressing in mice through ER stress-mediated apoptosis. J. Pharm. Pharmacol. 2023 75 5 645 654 10.1093/jpp/rgad008 36966363
    [Google Scholar]
  22. Yu X. Dai Y. Zhao Y. Qi S. Liu L. Lu L. Luo Q. Zhang Z. Melittin-lipid nanoparticles target to lymph nodes and elicit a systemic anti-tumor immune response. Nat. Commun. 2020 11 1 1110 10.1038/s41467‑020‑14906‑9 32111828
    [Google Scholar]
  23. Zhao L. Zhang H. Li N. Chen J. Xu H. Wang Y. Liang Q. Network pharmacology, a promising approach to reveal the pharmacology mechanism of Chinese medicine formula. J. Ethnopharmacol. 2023 309 116306 10.1016/j.jep.2023.116306 36858276
    [Google Scholar]
  24. Li L. Yang L. Yang L. He C. He Y. Chen L. Dong Q. Zhang H. Chen S. Li P. Network pharmacology: A bright guiding light on the way to explore the personalized precise medication of traditional Chinese medicine. Chin. Med. 2023 18 1 146 10.1186/s13020‑023‑00853‑2 37941061
    [Google Scholar]
  25. Yuan Z. Pan Y. Leng T. Chu Y. Zhang H. Ma J. Ma X. Progress and prospects of research ideas and methods in the network pharmacology of traditional Chinese medicine. J. Pharm. Pharm. Sci. 2022 25 218 226 10.18433/jpps32911 35760072
    [Google Scholar]
  26. Wang C. Liu X. Guo S. Network pharmacology-based strategy to investigate the effect and mechanism of α-solanine against glioma. BMC Complement. Med. Ther. 2023 23 1 371 10.1186/s12906‑023‑04215‑1 37865727
    [Google Scholar]
  27. Li X. Liu Z. Liao J. Chen Q. Lu X. Fan X. Network pharmacology approaches for research of traditional Chinese medicines. Chin. J. Nat. Med. 2023 21 5 323 332 10.1016/S1875‑5364(23)60429‑7 37245871
    [Google Scholar]
  28. Kim S. Thiessen P.A. Bolton E.E. Chen J. Fu G. Gindulyte A. Han L. He J. He S. Shoemaker B.A. Wang J. Yu B. Zhang J. Bryant S.H. PubChem substance and compound databases. Nucleic Acids Res. 2016 44 D1 D1202 D1213 10.1093/nar/gkv951 26400175
    [Google Scholar]
  29. Bateman A. Martin M-J. Orchard S. Magrane M. Ahmad S. Alpi E. Bowler-Barnett E.H. Britto R. Bye-A-Jee H. Cukura A. Denny P. Dogan T. Ebenezer T.G. Fan J. Garmiri P. da Costa Gonzales L.J. Hatton-Ellis E. Hussein A. Ignatchenko A. Insana G. Ishtiaq R. Joshi V. Jyothi D. Kandasaamy S. Lock A. Luciani A. Lugaric M. Luo J. Lussi Y. MacDougall A. Madeira F. Mahmoudy M. Mishra A. Moulang K. Nightingale A. Pundir S. Qi G. Raj S. Raposo P. Rice D.L. Saidi R. Santos R. Speretta E. Stephenson J. Totoo P. Turner E. Tyagi N. Vasudev P. Warner K. Watkins X. Zaru R. Zellner H. Bridge A.J. Aimo L. Argoud-Puy G. Auchincloss A.H. Axelsen K.B. Bansal P. Baratin D. Batista Neto T.M. Blatter M-C. Bolleman J.T. Boutet E. Breuza L. Gil B.C. Casals-Casas C. Echioukh K.C. Coudert E. Cuche B. de Castro E. Estreicher A. Famiglietti M.L. Feuermann M. Gasteiger E. Gaudet P. Gehant S. Gerritsen V. Gos A. Gruaz N. Hulo C. Hyka-Nouspikel N. Jungo F. Kerhornou A. Le Mercier P. Lieberherr D. Masson P. Morgat A. Muthukrishnan V. Paesano S. Pedruzzi I. Pilbout S. Pourcel L. Poux S. Pozzato M. Pruess M. Redaschi N. Rivoire C. Sigrist C.J.A. Sonesson K. Sundaram S. Wu C.H. Arighi C.N. Arminski L. Chen C. Chen Y. Huang H. Laiho K. McGarvey P. Natale D.A. Ross K. Vinayaka C.R. Wang Q. Wang Y. Zhang J. UniProt: The universal protein knowledgebase in 2023. Nucleic Acids Res. 2023 51 D1 D523 D531 10.1093/nar/gkac1052 36408920
    [Google Scholar]
  30. Wishart D.S. Feunang Y.D. Guo A.C. Lo E.J. Marcu A. Grant J.R. Sajed T. Johnson D. Li C. Sayeeda Z. Assempour N. Iynkkaran I. Liu Y. Maciejewski A. Gale N. Wilson A. Chin L. Cummings R. Le D. Pon A. Knox C. Wilson M. DrugBank 5.0: A major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 46 D1 D1074 D1082 10.1093/nar/gkx1037 29126136
    [Google Scholar]
  31. Safran M. Dalah I. Alexander J. Rosen N. Iny Stein T. Shmoish M. Nativ N. Bahir I. Doniger T. Krug H. Sirota-Madi A. Olender T. Golan Y. Stelzer G. Harel A. Lancet D. GeneCards Version 3: The human gene integrator. Database 2010 2010 0 baq020 10.1093/database/baq020 20689021
    [Google Scholar]
  32. Amberger J.S. Bocchini C.A. Schiettecatte F. Scott A.F. Hamosh A. OMIM.org: Online Mendelian Inheritance in Man (OMIM®), an online catalog of human genes and genetic disorders. Nucleic Acids Res. 2015 43 D1 D789 D798 10.1093/nar/gku1205 25428349
    [Google Scholar]
  33. Szklarczyk D. Franceschini A. Wyder S. Forslund K. Heller D. Huerta-Cepas J. Simonovic M. Roth A. Santos A. Tsafou K.P. Kuhn M. Bork P. Jensen L.J. von Mering C. STRING v10: Protein–protein interaction networks, integrated over the tree of life. Nucleic Acids Res. 2015 43 D1 D447 D452 10.1093/nar/gku1003 25352553
    [Google Scholar]
  34. Zhou Y. Zhou B. Pache L. Chang M. Khodabakhshi A.H. Tanaseichuk O. Benner C. Chanda S.K. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat. Commun. 2019 10 1 1523 10.1038/s41467‑019‑09234‑6 30944313
    [Google Scholar]
  35. Vivian J. Rao A.A. Nothaft F.A. Ketchum C. Armstrong J. Novak A. Pfeil J. Narkizian J. Deran A.D. Musselman-Brown A. Schmidt H. Amstutz P. Craft B. Goldman M. Rosenbloom K. Cline M. O’Connor B. Hanna M. Birger C. Kent W.J. Patterson D.A. Joseph A.D. Zhu J. Zaranek S. Getz G. Haussler D. Paten B. Toil enables reproducible, open source, big biomedical data analyses. Nat. Biotechnol. 2017 35 4 314 316 10.1038/nbt.3772 28398314
    [Google Scholar]
  36. Wang Y. Wang Y. Yuan C. Wang N. Zhang T. Naringin inhibits cisplatin resistance of ovarian cancer cells by inhibiting autophagy mediated by the TGF-β2/smad2 pathway. Transl. Cancer Res. 2024 13 6 2618 2628 10.21037/tcr‑23‑2156 38988927
    [Google Scholar]
  37. Wang Y. Xie L. Liu F. Ding D. Wei W. Han F. Research progress on traditional Chinese medicine-induced apoptosis signaling pathways in ovarian cancer cells. J. Ethnopharmacol. 2024 319 Pt 2 117299 10.1016/j.jep.2023.117299 37816474
    [Google Scholar]
  38. Cai J. Hu Q. He Z. Chen X. Wang J. Yin X. Ma X. Zeng J. Scutellaria baicalensis Georgi and their natural flavonoid compounds in the treatment of ovarian cancer: A review. Molecules 2023 28 13 5082 10.3390/molecules28135082 37446743
    [Google Scholar]
  39. Jo M. Park M.H. Kollipara P.S. An B.J. Song H.S. Han S.B. Kim J.H. Song M.J. Hong J.T. Anti-cancer effect of bee venom toxin and melittin in ovarian cancer cells through induction of death receptors and inhibition of JAK2/STAT3 pathway. Toxicol. Appl. Pharmacol. 2012 258 1 72 81 10.1016/j.taap.2011.10.009 22027265
    [Google Scholar]
  40. Liu M. Wang H. Liu L. Wang B. Sun G. Melittin-MIL-2 fusion protein as a candidate for cancer immunotherapy. J. Transl. Med. 2016 14 1 155 10.1186/s12967‑016‑0910‑0 27246873
    [Google Scholar]
  41. Guha S. Ferrie R.P. Ghimire J. Ventura C.R. Wu E. Sun L. Kim S.Y. Wiedman G.R. Hristova K. Wimley W.C. Applications and evolution of melittin, the quintessential membrane active peptide. Biochem. Pharmacol. 2021 193 114769 10.1016/j.bcp.2021.114769 34543656
    [Google Scholar]
  42. Lee M.T. Sun T.L. Hung W.C. Huang H.W. Process of inducing pores in membranes by melittin. Proc. Natl. Acad. Sci. USA 2013 110 35 14243 14248 10.1073/pnas.1307010110 23940362
    [Google Scholar]
  43. Oršolić N. Bee venom in cancer therapy. Cancer Metastasis Rev. 2012 31 1-2 173 194 10.1007/s10555‑011‑9339‑3 22109081
    [Google Scholar]
  44. Mondal S. Adhikari N. Banerjee S. Amin S.A. Jha T. Matrix metalloproteinase-9 (MMP-9) and its inhibitors in cancer: A minireview. Eur. J. Med. Chem. 2020 194 112260 10.1016/j.ejmech.2020.112260 32224379
    [Google Scholar]
  45. Chen L.H. Tsai Y.F. Wu W.T. Chiu K.L. Tsai C.W. Chang W.S. Li C.H. Yang J.S. Mong M.C. Hsia T.C. Bau D.T. Association of Matrix Metalloproteinase-9 genotypes with lung cancer risk in Taiwan. Anticancer Res. 2024 44 5 1845 1852 10.21873/anticanres.16986 38677770
    [Google Scholar]
  46. Chen C.H. Shih L.C. Hsu S.W. Tien H.C. Liu Y.F. Wang Y.C. Tsai C.W. Bau D.T. Chang W.S. Association of Matrix Metalloproteinase-9 genotypes with nasopharyngeal carcinoma risk. In Vivo 2024 38 4 1731 1739 10.21873/invivo.13623 38936920
    [Google Scholar]
  47. Liu C. Shen Y. Tan Q. Diagnostic and prognostic values of MMP-9 expression in ovarian cancer: A study based on bioinformatics analysis and meta-analysis. Int. J. Biol. Markers 2023 38 1 15 24 10.1177/03936155221140421 36448239
    [Google Scholar]
  48. Xu F. Si X. Wang J. Yang A. Qin T. Yang Y. Nectin-3 is a new biomarker that mediates the upregulation of MMP2 and MMP9 in ovarian cancer cells. Biomed. Pharmacother. 2019 110 139 144 10.1016/j.biopha.2018.11.020 30469078
    [Google Scholar]
  49. Pawar N.R. Buzza M.S. Duru N. Strong A.A. Antalis T.M. Matriptase drives dissemination of ovarian cancer spheroids by a PAR-2/PI3K/Akt/MMP9 signaling axis. J. Cell Biol. 2023 222 11 e202209114 10.1083/jcb.202209114 37737895
    [Google Scholar]
  50. Kamiya T. Mizuno N. Hayashi K. Otsuka T. Haba M. Abe N. Oyama M. Hara H. Methoxylated flavones from Casimiroa edulis La Llave suppress MMP9 expression via inhibition of the JAK/STAT3 pathway and TNFα-dependent pathways. J. Agric. Food Chem. 2024 72 26 14678 14683 10.1021/acs.jafc.4c00965 38910321
    [Google Scholar]
  51. Ma Q. Li X. Wang H. Xu S. Que Y. He P. Yang R. Wang Q. Hu Y. HOXB5 promotes the progression and metastasis of osteosarcoma cells by activating the JAK2/STAT3 signalling pathway. Heliyon 2024 10 9 e30445 10.1016/j.heliyon.2024.e30445 38737261
    [Google Scholar]
  52. Zhao Z. Bi B. Cheng G. Zhao Y. Wu H. Zheng M. Cao Z. Melatonin ameliorates osteoarthritis rat cartilage injury by inhibiting matrix metalloproteinases and JAK2/STAT3 signaling pathway. Inflammopharmacology 2023 31 1 359 368 10.1007/s10787‑022‑01102‑y 36427113
    [Google Scholar]
  53. El-Tanani M. Al Khatib A.O. Aladwan S.M. Abuelhana A. McCarron P.A. Tambuwala M.M. Importance of STAT3 signalling in cancer, metastasis and therapeutic interventions. Cell. Signal. 2022 92 110275 10.1016/j.cellsig.2022.110275 35122990
    [Google Scholar]
  54. Zou S. Tong Q. Liu B. Huang W. Tian Y. Fu X. Targeting STAT3 in cancer immunotherapy. Mol. Cancer 2020 19 1 145 10.1186/s12943‑020‑01258‑7 32972405
    [Google Scholar]
  55. Hu Y. Dong Z. Liu K. Unraveling the complexity of STAT3 in cancer: Molecular understanding and drug discovery. J. Exp. Clin. Cancer Res. 2024 43 1 23 10.1186/s13046‑024‑02949‑5 38245798
    [Google Scholar]
  56. He Z. Song B. Zhu M. Liu J. Comprehensive pan- cancer analysis of STAT3 as a prognostic and immunological biomarker. Sci. Rep. 2023 13 1 5069 10.1038/s41598‑023‑31226‑2 36977736
    [Google Scholar]
  57. Tan H. Wu C. Huang B. Jin L. Jiang X. MiR-3666 serves as a tumor suppressor in ovarian carcinoma by down-regulating AK4 via targeting STAT3. Cancer Biomark. 2021 30 4 355 363 10.3233/CBM‑190538 33361582
    [Google Scholar]
  58. Giordano M. Decio A. Battistini C. Baronio M. Bianchi F. Villa A. Bertalot G. Freddi S. Lupia M. Jodice M.G. Ubezio P. Colombo N. Giavazzi R. Cavallaro U. L1CAM promotes ovarian cancer stemness and tumor initiation via FGFR1/SRC/STAT3 signaling. J. Exp. Clin. Cancer Res. 2021 40 1 319 10.1186/s13046‑021‑02117‑z 34645505
    [Google Scholar]
  59. Wang A. Jin C. Tian X. Wang Y. Li H. Knockdown of HE4 suppresses aggressive cell growth and malignant progression of ovarian cancer by inhibiting the JAK/STAT3 pathway. Biol. Open 2019 8 9 bio043570 10.1242/bio.043570 31477564
    [Google Scholar]
  60. Liu Q. Li G. Li R. shen J. He Q. Deng L. Zhang C. Zhang J. IL-6 promotion of glioblastoma cell invasion and angiogenesis in U251 and T98G cell lines. J. Neurooncol. 2010 100 2 165 176 10.1007/s11060‑010‑0158‑0 20361349
    [Google Scholar]
  61. Alaaeldin R. Ali F.E.M. Bekhit A.A. Zhao Q.L. Fathy M. Inhibition of NF-kB/IL-6/JAK2/STAT3 pathway and epithelial-mesenchymal transition in breast cancer cells by Azilsartan. Molecules 2022 27 22 7825 10.3390/molecules27227825 36431925
    [Google Scholar]
  62. Li J. Zheng J. Lin B. Sun H. Lu S. Wang D. Huo H. Knockdown of NCAPG promotes the apoptosis and inhibits the invasion and migration of triple-negative breast cancer MDA-MB-231 cells via regulation of EGFR/JAK/STAT3 signaling. Exp. Ther. Med. 2023 25 3 119 10.3892/etm.2023.11818 36815969
    [Google Scholar]
  63. Liang Y. Li J. Xu H. Pang M. Hu C. Weng X. Xie W. Cepharanthine suppresses proliferation and metastasis and enhances apoptosis by regulating JAK2/Stat3 pathway in hepatocellular carcinoma. Cell. Mol. Biol. 2023 69 14 94 100 10.14715/cmb/2023.69.14.15 38279472
    [Google Scholar]
  64. Moga M. Dimienescu O. Arvătescu C. Ifteni P. Pleş L. Anticancer activity of toxins from bee and snake venom-An overview on ovarian cancer. Molecules 2018 23 3 692 10.3390/molecules23030692
    [Google Scholar]
  65. Lyu C. Fang F. Li B. Anti-tumor effects of melittin and its potential applications in clinic. Curr Protein Pept Sci. 2019 20 3 240 250 10.2174/1389203719666180612084615
    [Google Scholar]
  66. Zhou J. Wan C. Cheng J. Huang H. Lovell J.F. Jin H. Delivery strategies for melittin-based cancer therapy. ACS Appl. Mater. Interfaces 2021 13 15 17158 17173 10.1021/acsami.1c03640 33847113
    [Google Scholar]
  67. Kim S. Choi I. Han I.H. Bae H. Enhanced therapeutic effect of optimized Melittin-dKLA, a peptide agent targeting M2-like tumor-associated macrophages in triple-negative breast cancer. Int. J. Mol. Sci. 2022 23 24 15751 10.3390/ijms232415751 36555393
    [Google Scholar]
  68. Jia F. Chen P. Wang D. Sun Y. Ren M. Wang Y. Cao X. Zhang L. Fang Y. Tan X. Lu H. Cai J. Lu X. Zhang K. Bottlebrush polymer-conjugated melittin exhibits enhanced antitumor activity and better safety profile. ACS Appl Mater Interfaces. 2021 13 36 42533 42542 10.1021/acsami.1c14285
    [Google Scholar]
  69. Sahsuvar S. Guner R. Gok O. Can O. Development and pharmaceutical investigation of novel cervical cancer- targeting and redox-responsive melittin conjugates. Sci. Rep. 2023 13 1 18225 10.1038/s41598‑023‑45537‑x 37880286
    [Google Scholar]
  70. Choi M. Ryu J. Vu H.D. Kim D. Youn Y.J. Park M.H. Huynh P.T. Hwang G.B. Youn S.W. Jeong Y.H. Transferrin-conjugated melittin-loaded L-Arginine- coated iron oxide nanoparticles for mitigating beta-Amyloid pathology of the 5XFAD mouse brain. Int. J. Mol. Sci. 2023 24 19 14954 10.3390/ijms241914954 37834402
    [Google Scholar]
  71. Jin X. Wu H. Yu J. Cao Y. Zhang L. Zhang Z. Lv H. Glutamate affects self-assembly, protein corona, and anti-4 T1 tumor effects of melittin/vitamin E-succinic acid-(glutamate)n nanoparticles. J. Control. Release 2024 365 802 817 10.1016/j.jconrel.2023.12.013 38092255
    [Google Scholar]
  72. Akbarzadeh-Khiavi M. Torabi M. Olfati A.H. Rahbarnia L. Safary A. Bio-nano scale modifications of melittin for improving therapeutic efficacy. Expert Opin. Biol. Ther. 2022 22 7 895 909 10.1080/14712598.2022.2088277 35687355
    [Google Scholar]
  73. Fahmy U.A. Badr-Eldin S.M. Aldawsari H.M. Alhakamy N.A. Ahmed O.A.A. Radwan M.F. Eid B.G. Sayed S.R.M. El Sherbiny G.A. Abualsunun W. Potentiality of raloxifene loaded melittin functionalized lipidic nanovesicles against pancreatic cancer cells. Drug Deliv. 2022 29 1 1863 1877 10.1080/10717544.2022.2072544 35708464
    [Google Scholar]
  74. Laurindo L.F. de Lima E.P. Laurindo L.F. Rodrigues V.D. Chagas E.F.B. de Alvares Goulart R. Araújo A.C. Guiguer E.L. Pomini K.T. Rici R.E.G. Maria D.A. Direito R. Barbalho S.M. The therapeutic potential of bee venom-derived Apamin and Melittin conjugates in cancer treatment: A systematic review. Pharmacol. Res. 2024 209 107430 10.1016/j.phrs.2024.107430 39332751
    [Google Scholar]
  75. Wang A. Zheng Y. Zhu W. Yang L. Yang Y. Peng J. Melittin-based nano-delivery systems for cancer therapy. Biomolecules 2022 12 1 118 10.3390/biom12010118 35053266
    [Google Scholar]
  76. Wang H. Yang L. Liu R. He H. Zhang M. Xu Y. ADAR1 affects gastric cancer cell metastasis and reverses cisplatin resistance through AZIN1. Anticancer Drugs 2023 34 10 1132 1145 10.1097/CAD.0000000000001516 37104086
    [Google Scholar]
  77. Gao X. Zhang C. Wang Y. Zhang P. Zhang J. Hong T. Berberine and cisplatin exhibit synergistic anticancer effects on Osteosarcoma MG-63 cells by inhibiting the MAPK pathway. Molecules 2021 26 6 1666 10.3390/molecules26061666 33802664
    [Google Scholar]
  78. Mrkvicova A. Chmelarova M. Peterova E. Havelek R. Baranova I. Kazimirova P. Rudolf E. Rezacova M. The effect of sodium butyrate and cisplatin on expression of EMT markers. PLoS One 2019 14 1 e0210889 10.1371/journal.pone.0210889 30653577
    [Google Scholar]
  79. Alizadehnohi M. Nabiuni M. Nazari Z. Safaeinejad Z. Irian S. The synergistic cytotoxic effect of cisplatin and honey bee venom on human ovarian cancer cell line A2780cp. J. Venom Res. 2012 3 22 27 23301148
    [Google Scholar]
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Melittin Inhibits Ovarian Cancer Cell Growth by Downregulating MMP9 Expression via the JAK2-STAT3 Signaling Pathway
Bentham Science Publishers ; https://doi.org/10.2174/0109298673355946250403071132
/content/journals/cmc/10.2174/0109298673355946250403071132
/content/journals/cmc/10.2174/0109298673355946250403071132
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  • Article Type:     Research Article
Keywords: JAK-STAT signaling pathway ; matrix metalloproteinase 9 (MMP9) ; network pharmacology ; ovarian cancer ; Western blotting ; Melittin

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