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2000
Volume 32, Issue 33
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

Introduction

The effectiveness of therapy is strongly impacted by the resistance of lung cancer cells to cisplatin. The objective of this research is to characterize the impact of ailanthone on cisplatin resistance in non-small cell lung cancer (NSCLC) and examine any potential and in molecular pathways.

Methods

Following treatment of A549/DDP cells with ailanthone and cisplatin, cell survival and apoptosis were measured using flow cytometry and Cell Counting Kit-8 (CCK8) assays, respectively. mRFP-GFP-LC3 adenovirus transfection was used to track autophagy, and protein expression levels were analyzed by western blotting. Hematoxylin and eosin (H&E) staining was used after the organs of the mice were removed for investigations. In A549/DDP cells, ailanthone and cisplatin together induced autophagy and apoptosis in a dose and time-dependent manner (< 0.05). After receiving combined treatment with ailanthone and cisplatin, the expression levels of cleaved caspase-3, Bcl-2, cleaved PARP, Beclin 1, LC3B-II were considerably elevated by inhibiting the PI3K/AKT/mTOR signaling pathway.

Results

Our findings show that ailanthone, without causing adverse effects , greatly suppressed the growth of A549/DDP-grafted tumors and improved the anti-tumor efficaciousness of cisplatin.

Conclusion

According to this study, ailanthone may increase sensitivity to cisplatin and promote autophagy and death in NSCLC A549/DDP cells through the signaling pathway of PI3K/AKT/mTOR.

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2024-08-26
2025-10-01
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References

  1. HeydariF. RafsanjaniM. Corrigendum to: A review on lung cancer diagnosis using data mining algorithms.Curr. Med. Imaging Rev.202117567510.2174/15734056170521052716201934126890
    [Google Scholar]
  2. ToumazisI. BastaniM. HanS.S. PlevritisS.K. Risk-Based lung cancer screening: A systematic review.Lung Cancer202014715418610.1016/j.lungcan.2020.07.00732721652
    [Google Scholar]
  3. SankarK. GadgeelS.M. QinA. Molecular therapeutic targets in non-small cell lung cancer.Expert Rev. Anticancer Ther.202020864766110.1080/14737140.2020.178715632580596
    [Google Scholar]
  4. ManoharS. LeungN. Cisplatin nephrotoxicity: a review of the literature.J. Nephrol.2018311152510.1007/s40620‑017‑0392‑z28382507
    [Google Scholar]
  5. LiuH. LeeG. LeeJ.I. AhnT.G. KimS.A. Effects of genistein on anti-tumor activity of cisplatin in human cervical cancer cell lines.Obstet. Gynecol. Sci.201962532232810.5468/ogs.2019.62.5.32231538075
    [Google Scholar]
  6. XinM. GaoQ. XiangX. XuJ. JiaoY. LiX. ZhangX. JiaX. Autophagy inhibition enhances the anti-tumor activity of methylseleninic acid in cisplatin-resistance human lung adenocarcinoma cells.Front. Pharmacol.20221389097410.3389/fphar.2022.89097435592418
    [Google Scholar]
  7. [Makovec, T., 2019. Cisplatin and beyond: Molecular mechanisms of action and drug resistance development in cancer chemotherapy.Radiol. Oncol.201953
    [Google Scholar]
  8. AmableL. Cisplatin resistance and opportunities for precision medicine.Pharmacol. Res.2016106273610.1016/j.phrs.2016.01.00126804248
    [Google Scholar]
  9. GiacominiI. RagazziE. PasutG. MontopoliM. The pentose phosphate pathway and its involvement in cisplatin resistance.Int. J. Mol. Sci.202021393710.3390/ijms2103093732023830
    [Google Scholar]
  10. GaoY. LyuQ. LuoP. LiM. ZhouR. ZhangJ. LyuQ. Applications of machine learning to predict cisplatin resistance in lung cancer.Int. J. Gen. Med.2021145911592510.2147/IJGM.S32964434588799
    [Google Scholar]
  11. KryczkaJ. KryczkaJ. Czarnecka-ChrebelskaK.H. Brzeziańska-LasotaE. Molecular Mechanisms of Chemoresistance Induced by Cisplatin in NSCLC Cancer Therapy.Int. J. Mol. Sci.20212216888510.3390/ijms2216888534445588
    [Google Scholar]
  12. BaillyC. Anticancer properties and mechanism of action of the quassinoid ailanthone.Phytother. Res.20203492203221310.1002/ptr.668132239572
    [Google Scholar]
  13. WangC. LiH. WangX. LiW. SuQ. XiaoX. HaoT. ChenW. ZhangY. ZhangH. WuW. HuZ. ZhaoG. HuoM. HeY. ZhangC. Ailanthus altissima-derived ailanthone enhances gastric cancer cell apoptosis by inducing the repression of base excision repair by downregulating p23 expression.Int. J. Biol. Sci.202117112811282510.7150/ijbs.6067434345209
    [Google Scholar]
  14. NiZ. YaoC. ZhuX. GongC. XuZ. WangL. LiS. ZouC. ZhuS. Ailanthone inhibits non-small cell lung cancer cell growth through repressing DNA replication via downregulating RPA1.Br. J. Cancer2017117111621163010.1038/bjc.2017.31929024939
    [Google Scholar]
  15. ZhuoZ. HuJ. YangX. ChenM. LeiX. DengL. YaoN. PengQ. ChenZ. YeW. ZhangD. Ailanthone inhibits Huh7 cancer cell growth via cell cycle arrest and apoptosis in vitro and in vivo.Sci. Rep.2015511618510.1038/srep1618526525771
    [Google Scholar]
  16. DagaM. PizzimentiS. DianzaniC. CucciM.A. CavalliR. GrattarolaM. FerraraB. ScariotV. TrottaF. BarreraG. Ailanthone inhibits cell growth and migration of cisplatin resistant bladder cancer cells through down-regulation of Nrf2, YAP, and c-Myc expression.Phytomedicine20195615616410.1016/j.phymed.2018.10.03430668336
    [Google Scholar]
  17. CucciM.A. GrattarolaM. DianzaniC. DamiaG. RicciF. RoettoA. TrottaF. BarreraG. PizzimentiS. Ailanthone increases oxidative stress in CDDP-resistant ovarian and bladder cancer cells by inhibiting of Nrf2 and YAP expression through a post-translational mechanism.Free Radic. Biol. Med.202015012513510.1016/j.freeradbiomed.2020.02.02132101771
    [Google Scholar]
  18. TossettaG. MarzioniD. Natural and synthetic compounds in Ovarian Cancer: A focus on NRF2/KEAP1 pathway.Pharmacol. Res.202218310636510.1016/j.phrs.2022.10636535901941
    [Google Scholar]
  19. ChenL. WuC. WangH. ChenS. MaD. TaoY. WangX. LuanY. WangT. ShiY. SongG. ZhaoY. DongX. WangB. Analysis of long noncoding rnas in aila-induced non-small cell lung cancer inhibition.Front. Oncol.20211165256710.3389/fonc.2021.65256734235076
    [Google Scholar]
  20. StefaniC. MiricescuD. Stanescu-SpinuI.I. NicaR.I. GreabuM. TotanA.R. JingaM. Growth factors, pi3k/akt/mtor and mapk signaling pathways in colorectal cancer pathogenesis: Where are we now?Int. J. Mol. Sci.202122191026010.3390/ijms22191026034638601
    [Google Scholar]
  21. IksenP. Targeting the pi3k/akt/mtor signaling pathway in lung cancer: An update regarding potential drugs and natural products.Molecules202126134100
    [Google Scholar]
  22. ZhouJ. JiangY. Tanshinone I attenuates the malignant biological properties of ovarian cancer by inducing apoptosis and autophagy via the inactivation of PI3K/AKT/mTOR pathway.Cell Prolif.2020532e12739
    [Google Scholar]
  23. RongL. LiZ. LengX. LiH. MaY. ChenY. SongF. Salidroside induces apoptosis and protective autophagy in human gastric cancer AGS cells through the PI3K/Akt/mTOR pathway.Biomed. Pharmacother.202012210972610.1016/j.biopha.2019.10972631918283
    [Google Scholar]
  24. LiM. YangN. HaoL. ZhouW. LiL. LiuL. YangF. XuL. YaoG. ZhuC. XuW. FangS. Melatonin inhibits the ferroptosis pathway in rat bone marrow mesenchymal stem cells by activating the PI3K/AKT/mTOR signaling axis to attenuate steroid-induced osteoporosis.Oxid. Med. Cell. Longev.2022202212210.1155/2022/822373736035224
    [Google Scholar]
  25. MorelliA. TortelliT.Jr PavanI. SilvaF. GranatoD. PerucaG. PaulettiB. DominguesR. BezerraR. De MouraL. Paes LemeA. ChammasR. SimabucoF. Metformin impairs cisplatin resistance effects in A549 lung cancer cells through mTOR signaling and other metabolic pathways.Int. J. Oncol.20215862810.3892/ijo.2021.520833846781
    [Google Scholar]
  26. FuldaS. Tumor resistance to apoptosis.Int. J. Cancer2009124351151510.1002/ijc.2406419003982
    [Google Scholar]
  27. SmithA.G. MacleodK.F. Autophagy, cancer stem cells and drug resistance.J. Pathol.2019247570871810.1002/path.522230570140
    [Google Scholar]
  28. MortezaeeK. SalehiE. Mirtavoos-mahyariH. MotevaseliE. NajafiM. FarhoodB. RosengrenR.J. SahebkarA. Mechanisms of apoptosis modulation by curcumin: Implications for cancer therapy.J. Cell. Physiol.20192348125371255010.1002/jcp.2812230623450
    [Google Scholar]
  29. YuG. LuoH. ZhangN. WangY. LiY. HuangH. LiuY. HuY. LiuH. ZhangJ. TangY. HuangY. Loss of p53 sensitizes cells to palmitic acid-induced apoptosis by reactive oxygen species accumulation.Int. J. Mol. Sci.20192024626810.3390/ijms2024626831842349
    [Google Scholar]
  30. CarneiroB.A. El-DeiryW.S. Targeting apoptosis in cancer therapy.Nat. Rev. Clin. Oncol.202017739541710.1038/s41571‑020‑0341‑y32203277
    [Google Scholar]
  31. PistrittoG. TrisciuoglioD. CeciC. Alessia Garufi, D’Orazi, G., 2016. Apoptosis as anticancer mechanism: Function and dysfunction of its modulators and targeted therapeutic strategies.Aging201684603
    [Google Scholar]
  32. BadeB.C. Dela CruzC.S. Lung Cancer 2020.Clin. Chest Med.202041112410.1016/j.ccm.2019.10.00132008623
    [Google Scholar]
  33. NasimF. SabathB.F. EapenG.A. Lung Cancer.Med. Clin. North Am.2019103346347310.1016/j.mcna.2018.12.00630955514
    [Google Scholar]
  34. LiuW. Drug resistance to targeted therapeutic strategies in non-small cell lung cancer.Pharmacol. Ther.2020206107436
    [Google Scholar]
  35. DingH. YuX. HangC. GaoK. LaoX. JiaY. YanZ. Ailanthone: A novel potential drug for treating human cancer (Review).Oncol. Lett.20202021489150310.3892/ol.2020.1171032724391
    [Google Scholar]
  36. MaZ. ZhangW. WuY. ZhangM. WangL. WangY. WangY. LiuW. Cyclophilin A inhibits A549 cell oxidative stress and apoptosis by modulating the PI3K/Akt/mTOR signaling pathway.Biosci. Rep.2021411BSR2020321910.1042/BSR2020321933393627
    [Google Scholar]
  37. FangS. WanX. ZouX. SunS. HaoX. LiangC. ZhangZ. ZhangF. SunB. LiH. YuB. Arsenic trioxide induces macrophage autophagy and atheroprotection by regulating ROS-dependent TFEB nuclear translocation and AKT/mTOR pathway.Cell Death Dis.20211218810.1038/s41419‑020‑03357‑133462182
    [Google Scholar]
  38. SunR. ZhaiR. MaC. MiaoW. Combination of aloin and metformin enhances the antitumor effect by inhibiting the growth and invasion and inducing apoptosis and autophagy in hepatocellular carcinoma through PI3K/AKT/mTOR pathway.Cancer Med.2020931141115110.1002/cam4.272331830378
    [Google Scholar]
  39. SunY. ChenY. XuM. LiuC. ShangH. WangC. Shenmai injection supresses glycolysis and enhances cisplatin cytotoxicity in cisplatin-resistant A549/DDP cells via the AKT-mTOR-c-Myc signaling pathway.BioMed Res. Int.2020202011010.1155/2020/924368132685545
    [Google Scholar]
  40. SharmaA. ThakurR. MittalS. ShankarJ. Identification of high-risk single nucleotide polymorphisms (SNPs) of epidermal growth factor receptor (EGFR) and their interaction with various TKI drugs.Eurasian Journal of Medicine and Oncology2023202333434410.14744/ejmo.2023.33189
    [Google Scholar]
  41. ZhaoY. LiuJ. CaiX. PanZ. LiuJ. YinW. ChenH. XieZ. LiangH. WangW. GuoZ. ZhaoS. LiangW. HeJ. Efficacy and safety of first line treatments for patients with advanced epidermal growth factor receptor mutated, non-small cell lung cancer: systematic review and network meta-analysis.BMJ2019367l546010.1136/bmj.l546031591158
    [Google Scholar]
  42. LeonettiA. SharmaS. MinariR. PeregoP. GiovannettiE. TiseoM. Resistance mechanisms to osimertinib in EGFR-mutated non-small cell lung cancer.Br. J. Cancer2019121972573710.1038/s41416‑019‑0573‑831564718
    [Google Scholar]
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  • Article Type:
    Research Article
Keyword(s): ailanthone; apoptosis; autophagy; chemotherapy; drug resistance; Lung cancer
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