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2000
Volume 25, Issue 11
  • ISSN: 1871-5206
  • E-ISSN: 1875-5992

Abstract

Objective

The objective of this study is to examine the impact of KW2478 combined with DDP on colorectal cancer cells both and and to elucidate the molecular mechanism of KW2478 in colorectal cancer.

Methods

qRT-PCR and Western blot were employed to assess HSP90 mRNA and protein expression in normal intestinal epithelial and colorectal cancer cells. DLD-1 and HCT116 were selected for the experiment. CCK-8 was used to detect cytotoxicity; apoptosis rate was measured using flow cytometry; Western blot was employed to measure the expression levels of apoptotic and PI3K/AKT/mTOR pathway proteins. HCT116 was used to construct a subcutaneous tumor model in nude mice. After treatment with KW2478 and DDP, the growth rate, volume, and weight of the tumor were observed. The expression of Ki67 was detected by immunohistochemistry. Apoptosis of tumor cells was detected using TUNEL. Western blot was employed to measure the expression levels of apoptotic and PI3K/AKT/mTOR pathway proteins.

Results

HSP90 mRNA and protein levels were elevated in colorectal cancer cells compared to normal colorectal epithelial cells. HSP90 mRNA and protein expression levels were also significantly elevated in HCT116 and DLD-1 cells compared to other colorectal cancer cells. In DLD-1 and HCT116 cells, KW2478 and DDP inhibited cell viability. The combination of KW2478 and DDP exhibited a significantly higher inhibitory effect compared to either KW2478 or DDP alone. DDP markedly triggered apoptosis in HCT116 and DLD-1. KW2478 at 3 µg/ml and 6 µg/ml induced apoptosis in HCT116 cells but not in DLD-1 cells. The combination of KW2478 and DDP induced a significantly higher apoptosis rate as compared to either KW2478 or DDP alone. Treatment of HCT116 and DLD-1 with KW2478 or DDP alone increased Bax, Caspase9, and Caspase3 protein expression, and decreased BCL-2. The KW2478 + DDP combined treatment group exhibited more significant changes. Phosphorylation of PI3k, AKT, and mTOR decreased in the KW2478 or DDP treatment groups, with more significant changes observed in the KW2478 + DDP combination group. The growth rate, volume, and weight of subcutaneous tumors in the KW2478 or DDP treatment groups were significantly lower than control, and the KW2478 + DDP combination group was more affected. Ki67 expression in subcutaneous tumors was reduced in the KW2478 or DDP treatment groups compared to the vehicle control group, with the lowest expression observed in the KW2478 + DDP combination group. The fluorescence intensity of subcutaneous tumors was higher in both the KW2478 and DDP treatment groups compared to the vehicle control group, and the KW2478 + DDP combination group exhibited the strongest fluorescence intensity among them.

Conclusion

The combination of KW2478 and cisplatin inhibits colorectal cancer cell proliferation and induces apoptosis by regulating the PI3K/AKT/mTOR pathway.

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References

  1. IslamiF. Goding SauerA. MillerK.D. SiegelR.L. FedewaS.A. JacobsE.J. McCulloughM.L. PatelA.V. MaJ. SoerjomataramI. FlandersW.D. BrawleyO.W. GapsturS.M. JemalA. Proportion and number of cancer cases and deaths attributable to potentially modifiable risk factors in the United States.CA Cancer J. Clin.2018681315410.3322/caac.21440 29160902
     [Google Scholar]
  2. SiegelR.L. WagleN.S. CercekA. SmithR.A. JemalA. Colorectal cancer statistics, 2023.CA Cancer J. Clin.202373323325410.3322/caac.21772 36856579
     [Google Scholar]
  3. SinicropeF.A. Increasing incidence of early-onset colorectal cancer.N. Engl. J. Med.2022386161547155810.1056/NEJMra2200869 35443109
     [Google Scholar]
  4. SninskyJ.A. ShoreB.M. LupuG.V. CrockettS.D. Risk factors for colorectal polyps and cancer.Gastrointest. Endosc. Clin. N. Am.202232219521310.1016/j.giec.2021.12.008 35361331
     [Google Scholar]
  5. MurphyC.C. ZakiT.A. Changing epidemiology of colorectal cancer — birth cohort effects and emerging risk factors.Nat. Rev. Gastroenterol. Hepatol.2024211253410.1038/s41575‑023‑00841‑9 37723270
     [Google Scholar]
  6. BrozovicA. Ambriović-RistovA. OsmakM. The relationship between cisplatin-induced reactive oxygen species, glutathione, and BCL-2 and resistance to cisplatin.Crit. Rev. Toxicol.201040434735910.3109/10408441003601836 20163198
     [Google Scholar]
  7. WagnerJ.M. KarnitzL.M. Cisplatin-induced DNA damage activates replication checkpoint signaling components that differentially affect tumor cell survival.Mol. Pharmacol.200976120821410.1124/mol.109.055178 19403702
     [Google Scholar]
  8. KryczkaJ. KryczkaJ. Czarnecka-ChrebelskaK.H. Brzeziańska-LasotaE. Molecular mechanisms of chemoresistance induced by cisplatin in NSCLC cancer therapy.Int. J. Mol. Sci.20212216888510.3390/ijms22168885 34445588
     [Google Scholar]
  9. GalluzziL. SenovillaL. VitaleI. MichelsJ. MartinsI. KeppO. CastedoM. KroemerG. Molecular mechanisms of cisplatin resistance.Oncogene201231151869188310.1038/onc.2011.384 21892204
     [Google Scholar]
  10. KucukkayaB. BasogluH. ErdagD. AkbasF. SusgunS. YalcintepeL. Calcium homeostasis in cisplatin resistant epithelial ovarian cancer.Gen. Physiol. Biophys.201938435336310.4149/gpb_2019013 31241042
     [Google Scholar]
  11. WeaverD.A. CrawfordE.L. WarnerK.A. ElkhairiF. KhuderS.A. WilleyJ.C. ABCC5, ERCC2, XPA and XRCC1 transcript abundance levels correlate with cisplatin chemoresistance in non-small cell lung cancer cell lines.Mol. Cancer2005411810.1186/1476‑4598‑4‑18 15882455
     [Google Scholar]
  12. AloyzR. XuZ.Y. BelloV. BergeronJ. HanF.Y. YanY. MalapetsaA. Alaoui-JamaliM.A. DuncanA.M. PanasciL. Regulation of cisplatin resistance and homologous recombinational repair by the TFIIH subunit XPD.Cancer Res.2002621954575462 12359753
     [Google Scholar]
  13. ViguierJ. BoigeV. MiquelC. PocardM. GiraudeauB. SabourinJ.C. DucreuxM. SarasinA. PrazF. ERCC1 codon 118 polymorphism is a predictive factor for the tumor response to oxaliplatin/5-fluorouracil combination chemotherapy in patients with advanced colorectal cancer.Clin. Cancer Res.200511176212621710.1158/1078‑0432.CCR‑04‑2216 16144923
     [Google Scholar]
  14. WangQ. HuangC. WangD. TaoZ. ZhangH. ZhaoY. WangM. ZhouC. XuJ. ShenB. ZhuW. Gastric cancer derived mesenchymal stem cells promoted DNA repair and cisplatin resistance through up-regulating PD-L1/Rad51 in gastric cancer.Cell. Signal.202310611063910.1016/j.cellsig.2023.110639 36842523
     [Google Scholar]
  15. ZhouF. LuJ. JinW. LiZ. XuD. GuL. The role of USP51 in attenuating chemosensitivity of lung cancer cells to cisplatin by regulating DNA damage response.Biotechnol. Appl. Biochem.202370263464410.1002/bab.2386 35856403
     [Google Scholar]
  16. ZhangR. LiuS. GongB. XieW. ZhaoY. XuL. ZhengY. JinS. DingC. XuC. DongZ. Kif4A mediates resistance to neoadjuvant chemoradiotherapy in patients with advanced colorectal cancer via regulating DNA damage response.Acta Biochim. Biophys. Sin. (Shanghai)202254794095110.3724/abbs.2022068 35882623
     [Google Scholar]
  17. LiY. HuangH.Q. HuangZ.H. YuN.D. YeX.L. JiangM.C. ChenL.M. SNHG15 enhances cisplatin resistance in lung adenocarcinoma by affecting the DNA repair capacity of cancer cells.Diagn. Pathol.20231813310.1186/s13000‑023‑01291‑2 36864456
     [Google Scholar]
  18. YuanM. WuQ. ZhangM. LaiM. ChenW. YangJ. JiangL. CaoJ. Disulfiram enhances the antitumor activity of cisplatin by inhibiting the Fanconi anemia repair pathway.J. Zhejiang Univ. Sci. B202324320722010.1631/jzus.B2200405 36915997
     [Google Scholar]
  19. WhitesellL. LindquistS.L. HSP90 and the chaperoning of cancer.Nat. Rev. Cancer200551076177210.1038/nrc1716 16175177
     [Google Scholar]
  20. CsermelyP. SchnaiderT. SotiC. ProhászkaZ. NardaiG. The 90-kDa molecular chaperone family: Structure, function, and clinical applications. A comprehensive review.Pharmacol. Ther.199879212916810.1016/S0163‑7258(98)00013‑8 9749880
     [Google Scholar]
  21. HoterA. El-SabbanM.E. NaimH.Y. The HSP90 Family: Structure, regulation, function, and implications in health and disease.Int. J. Mol. Sci.2018199256010.3390/ijms19092560 30158430
     [Google Scholar]
  22. JohnsonJ.L. Evolution and function of diverse Hsp90 homologs and cochaperone proteins.Biochim. Biophys. Acta Mol. Cell Res.20121823360761310.1016/j.bbamcr.2011.09.020 22008467
     [Google Scholar]
  23. Subbarao SreedharA. KalmárÉ. CsermelyP. ShenY.F. Hsp90 isoforms: functions, expression and clinical importance.FEBS Lett.20045621-3111510.1016/S0014‑5793(04)00229‑7 15069952
     [Google Scholar]
  24. XuQ. TuJ. DouC. ZhangJ. YangL. LiuX. LeiK. LiuZ. WangY. LiL. BaoH. WangJ. TuK. HSP90 promotes cell glycolysis, proliferation and inhibits apoptosis by regulating PKM2 abundance via Thr-328 phosphorylation in hepatocellular carcinoma.Mol. Cancer201716117810.1186/s12943‑017‑0748‑y 29262861
     [Google Scholar]
  25. ReganP.L. JacobsJ. WangG. TorresJ. EdoR. FriedmannJ. TangX.X. HSP90 inhibition increases p53 expression and destabilizes MYCN and MYC in neuroblastoma.Int. J. Oncol.2011381105112 21109931
     [Google Scholar]
  26. ChuS. LiuY. ZhangL. LiuB. LiL. ShiJ. LiL. Regulation of survival and chemoresistance by HSP90AA1 in ovarian cancer SKOV3 cells.Mol. Biol. Rep.20134011610.1007/s11033‑012‑1930‑3 23135731
     [Google Scholar]
  27. EustaceB.K. SakuraiT. StewartJ.K. YimlamaiD. UngerC. ZehetmeierC. LainB. TorellaC. HenningS.W. BesteG. ScrogginsB.T. NeckersL. IlagL.L. JayD.G. Functional proteomic screens reveal an essential extracellular role for HSP90α in cancer cell invasiveness.Nat. Cell Biol.20046650751410.1038/ncb1131 15146192
     [Google Scholar]
  28. BuffartT.E. CarvalhoB. GriekenN.C.T. WieringenW.N. TijssenM. KranenbargE.M.K. VerheulH.M.W. GrabschH.I. YlstraB. VeldeC.J.H. MeijerG.A. Losses of chromosome 5q and 14q are associated with favorable clinical outcome of patients with gastric cancer.Oncologist201217565366210.1634/theoncologist.2010‑0379 22531355
     [Google Scholar]
  29. NakashimaT. IshiiT. TagayaH. SeikeT. NakagawaH. KandaY. AkinagaS. SogaS. ShiotsuY. New molecular and biological mechanism of antitumor activities of KW-2478, a novel nonansamycin heat shock protein 90 inhibitor, in multiple myeloma cells.Clin. Cancer Res.201016102792280210.1158/1078‑0432.CCR‑09‑3112 20406843
     [Google Scholar]
  30. YongK. CavetJ. JohnsonP. MorganG. WilliamsC. NakashimaD. AkinagaS. OakerveeH. CavenaghJ. Phase I study of KW-2478, a novel HSP90 inhibitor, in patients with B-cell malignancies.Br. J. Cancer2016114171310.1038/bjc.2015.422 26695442
     [Google Scholar]
  31. ChangX. ZhaoX. WangJ. DingS. XiaoL. ZhaoE. ZhengX. Effect of HSP90 inhibitor KW-2478 on HepG2 cells.Anticancer. Agents Med. Chem.202019182231224210.2174/1871520619666191023094610 31642416
     [Google Scholar]
  32. TabataM. TsubakiM. TakedaT. TateishiK. MaekawaS. TsurushimaK. ImanoM. SatouT. IshizakaT. NishidaS. Inhibition of HSP90 overcomes melphalan resistance through downregulation of Src in multiple myeloma cells.Clin. Exp. Med.2020201637110.1007/s10238‑019‑00587‑2 31650359
     [Google Scholar]
  33. JuríkováM. DanihelĽ. PolákŠ. VargaI. Ki67, PCNA, and MCM proteins: Markers of proliferation in the diagnosis of breast cancer.Acta Histochem.2016118554455210.1016/j.acthis.2016.05.002 27246286
     [Google Scholar]
  34. IatropoulosM.J. WilliamsG.M. Proliferation markers.Exp. Toxicol. Pathol.1996482-317518110.1016/S0940‑2993(96)80039‑X 8672872
     [Google Scholar]
  35. KanitkisJ. NarvaezD. EuvrardS. FaureM. ClaudyA. Proliferation markers Ki67 and PCNA in cutaneous squamous cell carcinomas: lack of prognostic value.Br. J. Dermatol.1997136464364410.1111/j.1365‑2133.1997.tb02173.x 9155986
     [Google Scholar]
  36. KyrylkovaK. KyryachenkoS. LeidM. KioussiC. Detection of apoptosis by TUNEL assay.Methods Mol. Biol.2012887414710.1007/978‑1‑61779‑860‑3_5 22566045
     [Google Scholar]
  37. DuanW.R. GarnerD.S. WilliamsS.D. Funckes-ShippyC.L. SpathI.S. BlommeE.A.G. Comparison of immunohistochemistry for activated caspase‐3 and cleaved cytokeratin 18 with the TUNEL method for quantification of apoptosis in histological sections of PC‐3 subcutaneous xenografts.J. Pathol.2003199222122810.1002/path.1289 12533835
     [Google Scholar]
  38. SiegelR.L. MillerK.D. FedewaS.A. AhnenD.J. MeesterR.G.S. BarziA. JemalA. Colorectal cancer statistics, 2017.CA Cancer J. Clin.201767317719310.3322/caac.21395 28248415
     [Google Scholar]
  39. FalconeA. RicciS. BrunettiI. PfannerE. AllegriniG. BarbaraC. CrinòL. BenedettiG. EvangelistaW. FanchiniL. CortesiE. PiconeV. VitelloS. ChiaraS. GranettoC. PorcileG. FiorettoL. OrlandiniC. AndreuccettiM. MasiG. Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: The Gruppo Oncologico Nord Ovest.J. Clin. Oncol.200725131670167610.1200/JCO.2006.09.0928 17470860
     [Google Scholar]
  40. FuchsC.S. MarshallJ. MitchellE. WierzbickiR. GanjuV. JefferyM. SchulzJ. RichardsD. Soufi-MahjoubiR. WangB. BarruecoJ. Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: Results from the BICC-C Study.J. Clin. Oncol.200725304779478610.1200/JCO.2007.11.3357 17947725
     [Google Scholar]
  41. TangY.L. LiD.D. DuanJ.Y. ShengL.M. WangX. Resistance to targeted therapy in metastatic colorectal cancer: Current status and new developments.World J. Gastroenterol.202329692694810.3748/wjg.v29.i6.926 36844139
     [Google Scholar]
  42. ZengD. GaoM. ZhengR. QinR. HeW. LiuS. WeiW. HuangZ. The HSP90 inhibitor KW-2478 depletes the malignancy of BCR/ABL and overcomes the imatinib-resistance caused by BCR/ABL amplification.Exp. Hematol. Oncol.20221113310.1186/s40164‑022‑00287‑w 35624462
     [Google Scholar]
  43. LiH.J. WangQ.S. HanW. ZhouH. LiP. ZhouF. QinW. ZhaoD. ZhouX. HeC.X. XingL. LiP.Q. JinX. YuF. HeJ.H. CaoH.L. Anti-NSCLC activity in vitro of HSP90N inhibitor KW-2478 and complex crystal structure determination of HSP90N-KW-2478.J. Struct. Biol.2021213210771010.1016/j.jsb.2021.107710 33610655
     [Google Scholar]
  44. WongR.S.Y. Apoptosis in cancer: from pathogenesis to treatment.J. Exp. Clin. Cancer Res.20113018710.1186/1756‑9966‑30‑87 21943236
     [Google Scholar]
  45. KashyapD. GargV.K. GoelN. Intrinsic and extrinsic pathways of apoptosis: Role in cancer development and prognosis.Adv. Protein Chem. Struct. Biol.20211257312010.1016/bs.apcsb.2021.01.003 33931145
     [Google Scholar]
  46. MohammadR.M. MuqbilI. LoweL. YedjouC. HsuH.Y. LinL.T. SiegelinM.D. FimognariC. KumarN.B. DouQ.P. YangH. Broad targeting of resistance to apoptosis in cancer.Semin. Cancer Biol.201535S78S10310.1016/j.semcancer.2015.03.001
     [Google Scholar]
  47. BremerE. van DamG. KroesenB.J. de LeijL. HelfrichW. Targeted induction of apoptosis for cancer therapy: Current progress and prospects.Trends Mol. Med.200612838239310.1016/j.molmed.2006.06.002 16798087
     [Google Scholar]
  48. ChristgenS. TweedellR.E. KannegantiT.D. Programming inflammatory cell death for therapy.Pharmacol. Ther.202223210801010.1016/j.pharmthera.2021.108010 34619283
     [Google Scholar]
  49. VahidiR. SafiS. FarsinejadA. PanahiN. Citrate and celecoxib induce apoptosis and decrease necrosis in synergistic manner in canine mammary tumor cells.Cell. Mol. Biol.20156152228 26475384
     [Google Scholar]
  50. HardwickJ.M. SoaneL. Multiple functions of BCL-2 family proteins.Cold Spring Harb. Perspect. Biol.201352a00872210.1101/cshperspect.a008722 23378584
     [Google Scholar]
  51. HafeziS. RahmaniM. Targeting BCL-2 in cancer: Advances, challenges, and perspectives.Cancers (Basel)2021136129210.3390/cancers13061292 33799470
     [Google Scholar]
  52. SpitzA.Z. GavathiotisE. Physiological and pharmacological modulation of BAX.Trends Pharmacol. Sci.202243320622010.1016/j.tips.2021.11.001 34848097
     [Google Scholar]
  53. SamiaS. Sandeep CharyP. KhanO. Kumar MehraN. Recent trends and advances in novel formulations as an armament in Bcl-2/Bax targeted breast cancer.Int. J. Pharm.202465312388910.1016/j.ijpharm.2024.123889 38346605
     [Google Scholar]
  54. RaisovaM. HossiniA.M. EberleJ. RiebelingC. OrfanosC.E. GeilenC.C. WiederT. SturmI. DanielP.T. The Bax/Bcl-2 ratio determines the susceptibility of human melanoma cells to CD95/Fas-mediated apoptosis.J. Invest. Dermatol.2001117233334010.1046/j.0022‑202x.2001.01409.x 11511312
     [Google Scholar]
  55. ProkopA. WiederT. SturmI. EβmannF. SeegerK. WuchterC. LudwigW-D. HenzeG. DörkenB. DanielP.T. Relapse in childhood acute lymphoblastic leukemia is associated with a decrease of the Bax/Bcl-2 ratio and loss of spontaneous caspase-3 processing in vivo.Leukemia20001491606161310.1038/sj.leu.2401866 10995007
     [Google Scholar]
  56. KimR. EmiM. TanabeK. Caspase-dependent and -independent cell death pathways after DNA damage (Review).Oncol. Rep.200514359559910.3892/or.14.3.595 16077961
     [Google Scholar]
  57. KolenkoV.M. UzzoR.G. BukowskiR. FinkeJ.H. Caspase-dependent and -independent death pathways in cancer therapy.Apoptosis200051172010.1023/A:1009677307458 11227486
     [Google Scholar]
  58. EstaquierJ. ValletteF. VayssiereJ.L. MignotteB. The mitochondrial pathways of apoptosis.Adv. Exp. Med. Biol.201294215718310.1007/978‑94‑007‑2869‑1_7 22399422
     [Google Scholar]
  59. NarayanankuttyA. PI3K/Akt/mTOR pathway as a therapeutic target for colorectal cancer: A review of preclinical and clinical evidence.Curr. Drug Targets201920121217122610.2174/1389450120666190618123846 31215384
     [Google Scholar]
  60. MoafianZ. MaghrouniA. SoltaniA. HashemyS.I. Cross-talk between non-coding RNAs and PI3K/AKT/mTOR pathway in colorectal cancer.Mol. Biol. Rep.20214854797481110.1007/s11033‑021‑06458‑y 34057685
     [Google Scholar]
  61. FangJ.Y. RichardsonB.C. The MAPK signalling pathways and colorectal cancer.Lancet Oncol.20056532232710.1016/S1470‑2045(05)70168‑6 15863380
     [Google Scholar]
  62. LechG. SłotwińskiR. SłodkowskiM. KrasnodębskiI.W. Colorectal cancer tumour markers and biomarkers: Recent therapeutic advances.World J. Gastroenterol.20162251745175510.3748/wjg.v22.i5.1745 26855534
     [Google Scholar]
  63. WeiR. XiaoY. SongY. YuanH. LuoJ. XuW. FAT4 regulates the EMT and autophagy in colorectal cancer cells in part via the PI3K-AKT signaling axis.J. Exp. Clin. Cancer Res.201938111210.1186/s13046‑019‑1043‑0 30832706
     [Google Scholar]
  64. PanduranganA.K. Potential targets for prevention of colorectal cancer: a focus on PI3K/Akt/mTOR and Wnt pathways.Asian Pac. J. Cancer Prev.20131442201220510.7314/APJCP.2013.14.4.2201 23725112
     [Google Scholar]
  65. ChengH. JiangX. ZhangQ. MaJ. ChengR. YongH. ShiH. ZhouX. GeL. GaoG. Naringin inhibits colorectal cancer cell growth by repressing the PI3K/AKT/mTOR signaling pathway.Exp. Ther. Med.20201963798380410.3892/etm.2020.8649 32346444
     [Google Scholar]
  66. Giulino-RothL. van BesienH.J. DaltonT. TotonchyJ.E. RodinaA. TaldoneT. BolaenderA. Erdjument-BromageH. SadekJ. ChadburnA. BarthM.J. Dela CruzF.S. RaineyA. KungA.L. ChiosisG. CesarmanE. Inhibition of HSP90 suppresses PI3K/AKT/mTOR signaling and has antitumor activity in burkitt lymphoma.Mol. Cancer Ther.20171691779179010.1158/1535‑7163.MCT‑16‑0848 28619753
     [Google Scholar]
  67. WuY.W. ChaoM.W. TuH.J. ChenL.C. HsuK.C. LiouJ.P. YangC.R. YenS.C. HuangFu, W.C.; Pan, S.L. A novel dual HDAC and HSP90 inhibitor, MPT0G449, downregulates oncogenic pathways in human acute leukemia in vitro and in vivo.Oncogenesis20211053910.1038/s41389‑021‑00331‑0 33986242
     [Google Scholar]
  68. LeeS.H. JeeJ.G. BaeJ.S. LiuK.H. LeeY.M. A group of novel HIF-1α inhibitors, glyceollins, blocks HIF-1α synthesis and decreases its stability via inhibition of the PI3K/AKT/mTOR pathway and HSP90 binding.J. Cell. Physiol.2015230485386210.1002/jcp.24813 25204544
     [Google Scholar]
  69. ChenM.H. ChiangK.C. ChengC.T. HuangS.C. ChenY.Y. ChenT.W. YehT.S. JanY.Y. WangH.M. WengJ.J. ChangP.M.H. LiuC.Y. LiC.P. ChaoY. ChenM.H. HuangC.Y.F. YehC.N. Antitumor activity of the combination of an HSP90 inhibitor and a PI3K/mTOR dual inhibitor against cholangiocarcinoma.Oncotarget2014592372238910.18632/oncotarget.1706 24796583
     [Google Scholar]
  70. PanZ. ChenY. PangH. WangX. ZhangY. XieX. HeG. Design, synthesis, and biological evaluation of novel dual inhibitors of heat shock protein 90/mammalian target of rapamycin (HSP90/mTOR) against bladder cancer cells.Eur. J. Med. Chem.202224211467410.1016/j.ejmech.2022.114674 35987020
     [Google Scholar]
  71. CaleroR. MorchonE. Martinez-ArgudoI. SerranoR. Synergistic anti-tumor effect of 17AAG with the PI3K/mTOR inhibitor NVP-BEZ235 on human melanoma.Cancer Lett.201740611110.1016/j.canlet.2017.07.021 28774796
     [Google Scholar]
  72. GloesenkampC. NitzscheB. LimA.R. NormantE. VosburghE. SchraderM. OckerM. ScherüblH. HöpfnerM. Heat shock protein 90 is a promising target for effective growth inhibition of gastrointestinal neuroendocrine tumors.Int. J. Oncol.201240516591667 22246317
     [Google Scholar]
  73. LiG. ZhangC. LiangW. ZhangY. ShenY. TianX. Berberine regulates the Notch1/PTEN/PI3K/AKT/mTOR pathway and acts synergistically with 17-AAG and SAHA in SW480 colon cancer cells.Pharm. Biol.2021591213010.1080/13880209.2020.1865407 33417512
     [Google Scholar]
  74. KimS.H. KangJ.G. KimC.S. IhmS.H. ChoiM.G. YooH.J. LeeS.J. Synergistic cytotoxicity of BIIB021 with triptolide through suppression of PI3K/Akt/mTOR and NF-κB signal pathways in thyroid carcinoma cells.Biomed. Pharmacother.201683223210.1016/j.biopha.2016.06.014 27470546
     [Google Scholar]
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KW2478 and Cisplatin Synergistically Anti-colorectal Cancer by Targeting PI3K/AKT/mTOR Pathway
Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents) 25, 800 (2025); https://doi.org/10.2174/0118715206356311241128075924
/content/journals/acamc/10.2174/0118715206356311241128075924
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  • Article Type:     Research Article
Keyword(s): AKT; colorectal cancer; DDP; KW2478; mTOR; PI3K

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