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Volume 24, Issue 18
  • ISSN: 1871-5206
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Abstract

Background

Cisplatin is a key therapeutic agent for bladder cancer, yet the emergence of cisplatin resistance presents a significant clinical challenge.

Objective

This study aims to investigate the potential and mechanisms of cyclanoline (Cyc) in overcoming cisplatin resistance.

Methods

Cisplatin-resistant T24 and BIU-87 cell models (T24/DR and BIU-87/DR) were established by increasing gradual concentration. Western Blot (WB) assessed the phosphorylation of STAT3, JAK2, and JAK3. T24/DR and BIU-87/DR cell lines were treated with selective STAT3 phosphorylation modulators, and cell viability was evaluated by CCK-8. Cells were subjected to cisplatin, Cyc, or their combination. Immunofluorescence (IHC) examined p-STAT3 expression. Protein and mRNA levels of apoptosis-related and cell cycle-related factors were measured. Changes in proliferation, invasion, migration, apoptosis, and cell cycle were monitored. , subcutaneous tumor transplantation models in nude mice were established, assessing tumor volume and weight. Changes in bladder cancer tissues were observed through HE staining, and the p-STAT3 was assessed WB and IHC.

Results

Cisplatin-resistant cell lines were successfully established, demonstrating increased phosphorylation of STAT3, JAK2, and JAK3. Cisplatin or Cyc treatment decreased p-STAT3, inhibited invasion and migration, and induced apoptosis and cell cycle arrest in the G0/G1 phase . , tumor growth was significantly suppressed, with extensive tumor cell death. IHC and WB consistently showed a substantial downregulation of STAT3 phosphorylation. These changes were more pronounced when cisplatin and Cyc were administered in combination.

Conclusion

Cyc reverses cisplatin resistance JAK/STAT3 inhibition in bladder cancer, offering a potential clinical strategy to enhance cisplatin efficacy in treating bladder cancer.

© 2024 Bentham Science Publishers
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2024-11-01
2024-11-29

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References

  1. DobruchJ. OszczudłowskiM. Bladder cancer: Current challenges and future directions.Medicina (Kaunas)202157874910.3390/medicina57080749
     [Google Scholar]
  2. FacchiniG. CavaliereC. RomisL. MordenteS. FacchiniS. IovaneG. CapassoM. D’ErricoD. LiguoriC. FormatoR. CicalaS. AndreozziF. Di LauroG. ImbimboC. VanniM. D’AnielloC. Advanced/metastatic bladder cancer: Current status and future directions.Eur. Rev. Med. Pharmacol. Sci.20202422115361155210.26355/eurrev_202011_23795
     [Google Scholar]
  3. SeidlC. Targets for therapy of bladder cancer.Semin Nucl Med202050216217010.1053/j.semnuclmed.2020.02.006
     [Google Scholar]
  4. HuX. LiJ. FuM. ZhaoX. WangW. The JAK/STAT signaling pathway: From bench to clinic.Signal Transduct. Target. Ther.20216140210.1038/s41392‑021‑00791‑1
     [Google Scholar]
  5. OwenK.L. BrockwellN.K. ParkerB.S. AK-STAT signaling: A double-edged sword of immune regulation and cancer progression.Cancers (Basel)20191112200210.3390/cancers11122002
     [Google Scholar]
  6. StevensL.E. PeluffoG. QiuX. TemkoD. FasslA. LiZ. TrinhA. SeehawerM. JovanovićB. AlečkovićM. WildeC.M. GeckR.C. ShuS. KingstonN.L. HarperN.W. AlmendroV. PykeA.L. EgriS.B. PapanastasiouM. ClementK. ZhouN. WalkerS. SalasJ. ParkS.Y. FrankD.A. MeissnerA. JaffeJ.D. SicinskiP. TokerA. MichorF. LongH.W. OvermoyerB.A. PolyakK. JAK–STAT signaling in inflammatory breast cancer enables Chemotherapy-Resistant cell states.Cancer Res.202383226428410.1158/0008‑5472.CAN‑22‑0423
     [Google Scholar]
  7. LimbergJ. EganC.E. GrayK.D. SinghM. LoewensteinZ. YangY. RiascosM.C. Al AsadiH. SafeP. El EshakyS. LiangH. UllmannT.M. WangW. LiW. ZhangT. XiangJ. StefanovaD. JinM.M. ZarnegarR. FaheyT.J. MinI.M. Activation of the JAK/STAT pathway leads to braf inhibitor resistance in BRAFV600E positive thyroid carcinoma.Mol. Cancer Res.202321539741010.1158/1541‑7786.MCR‑21‑0832
     [Google Scholar]
  8. BeiY. ChenX. XuQ. LvJ. HuJ. YangS. Apatinib weakens resistance of gastric cancer cells to paclitaxel by suppressing JAK/STAT3 signaling pathway.Drug Dev. Res.202283237938810.1002/ddr.21867
     [Google Scholar]
  9. PatelM.R. DashA. JacobsonB.A. JiY. BaumannD. IsmailK. KratzkeR.A. AK/STAT inhibition with ruxolitinib enhances oncolytic virotherapy in non-small cell lung cancer models.Cancer Gene Ther.20192611-1241141810.1038/s41417‑018‑0074‑6
     [Google Scholar]
  10. LiY. ShanZ. LiuC. YangD. WuJ. MenC. XuY. MicroRNA-294 promotes cellular proliferation and motility through the PI3K/AKT and JAK/STAT pathways by upregulation of NRAS in bladder cancer.Biochemistry (Mosc.)201782447448210.1134/S0006297917040095
     [Google Scholar]
  11. HuangW. LiY. ZhangC. ZhaH. ZhouX. FuB. GuoJ. WangG. IGF2BP3 facilitates cell proliferation and tumorigenesis via modulation of JAK/STAT signalling pathway in human bladder cancer.J. Cell. Mol. Med.20202423139491396010.1111/jcmm.16003
     [Google Scholar]
  12. ZhangY. QiD. GaoY. LiangC. ZhangY. MaZ. LiuY. PengH. ZhangY. QinH. SongX. SunX. LiY. LiuZ. History of uses, phytochemistry, pharmacological activities, quality control and toxicity of the root of Stephania tetrandra S. Moore: A review.J. Ethnopharmacol.202026011299510.1016/j.jep.2020.112995
     [Google Scholar]
  13. JiangY. LiuM. LiuH. LiuS. A critical review: Traditional uses, phytochemistry, pharmacology and toxicology of Stephania tetrandra S. Moore (Fen Fang Ji).Phytochem. Rev.202019244948910.1007/s11101‑020‑09673‑w
     [Google Scholar]
  14. ZhangY. LiuW. HeW. ZhangY. DengX. MaY. ZengJ. KouB. Tetrandrine reverses epithelial-mesenchymal transition in bladder cancer by downregulating Gli-1.Int. J. Oncol.20164852035204210.3892/ijo.2016.3415
     [Google Scholar]
  15. FanB. ZhangX. MaY. ZhangA. Fangchinoline induces apoptosis, autophagy and energetic impairment in bladder cancer.Cell. Physiol. Biochem.20174331003101110.1159/000481698
     [Google Scholar]
  16. LiJ. LiL. ZhuJ. ChenH. Effect and mechanism of cyclanoline on nitrosamine-induced bladder cancer in rats.Chin. Tradit. Herb. Drugs.202052015206
     [Google Scholar]
  17. KongX.P. RenH.Q. LiuE.Y.L. LeungK.W. GuoS.C. DuanR. DongT.T.X. TsimK.W.K. The cholinesterase inhibitory properties of Stephaniae tetrandrae radix.Molecules20202524591410.3390/molecules25245914
     [Google Scholar]
  18. LiF. ZhengZ. ChenW. LiD. ZhangH. ZhuY. MoQ. ZhaoX. FanQ. DengF. HanC. TanW. Regulation of cisplatin resistance in bladder cancer by epigenetic mechanisms.Drug Resist. Updat.20236810093810.1016/j.drup.2023.100938
     [Google Scholar]
  19. HuangB. LangX. LiX. The role of IL-6/JAK2/STAT3 signaling pathway in cancers.Front. Oncol.202212102317710.3389/fonc.2022.1023177
     [Google Scholar]
  20. XuB. ChenX. TanJ. XuX. Effect of AG490 on JAK2/STAT3 signaling pathway in human retinoblastoma HXO-RB44 cell lines.Zhong Nan Da Xue Xue Bao Yi Xue Ban201843101061106710.11817/j.issn.1672‑7347.2018.10.004
     [Google Scholar]
  21. ChenZ. DuY. LiuX. ChenH. WengX. GuoJ. WangM. WangX. WangL. EZH2 inhibition suppresses bladder cancer cell growth and metastasis via the JAK2/STAT3 signaling pathway.Oncol. Lett.201918190791510.3892/ol.2019.10359
     [Google Scholar]
  22. WangH. MaY. β-Elemene alleviates cisplatin resistance in oral squamous cell carcinoma cell via inhibiting JAK2/STAT3 pathway in vitro and in vivo.Cancer Cell Int.202222124410.1186/s12935‑022‑02650‑7
     [Google Scholar]
  23. HuX. MaJ. VikashV. LiJ. WuD. LiuY. ZhangJ. DongW. Thymoquinone augments cisplatin-induced apoptosis on esophageal carcinoma through mitigating the activation of JAK2/STAT3 pathway.Dig. Dis. Sci.201863112613410.1007/s10620‑017‑4856‑8
     [Google Scholar]
  24. ZhongY. LeF. ChengJ. LuoC. ZhangX. WuX. XuF. ZuoQ. TanB. Triptolide inhibits JAK2/STAT3 signaling and induces lethal autophagy through ROS generation in cisplatin resistant SKOV3/DDP ovarian cancer cells.Oncol. Rep.20214556910.3892/or.2021.8020
     [Google Scholar]
  25. NooriS. NourbakhshM. FarzanehS. ZarghiA. A ferrocene derivative reduces cisplatin resistance in breast cancer cells through suppression of MDR-1 expression and modulation of JAK2/STAT3 signaling pathway.Anticancer. Agents Med. Chem.202020182285229210.2174/1871520620666200807103903
     [Google Scholar]
  26. ShiL. ShuY. HuX. AkramW. WangJ. DongS. LuoB. ZhangJ. HuS. LiX. HuX. An optimized two-herb chinese food as medicine formula reduces cisplatin-induced nephrotoxicity in the treatment of lung cancer in mice.Front. Pharmacol.20221382790110.3389/fphar.2022.827901
     [Google Scholar]
  27. DasariS. NjikiS. MbemiA. YedjouC.G. TchounwouP.B. Pharmacological effects of cisplatin combination with natural products in cancer chemotherapy.Int. J. Mol. Sci.2022233153210.3390/ijms23031532
     [Google Scholar]
  28. ChenY. HongC. ChenX. QinZ. Demethoxycurcumin increases the sensitivity of cisplatin-resistant non-small lung cancer cells to cisplatin and induces apoptosis by activating the caspase signaling pathway.Oncol. Lett.202020520910.3892/ol.2020.12072
     [Google Scholar]
  29. LeiT. ZhouS. MengQ. ZhangM. STAT3 signaling pathway in drug-resistant bladder cancer cell line.J. Biol. Regul. Homeost. Agents20193351347135710.23812/19‑68‑A
     [Google Scholar]
  30. HuangH. FanX. ZhangX. XieY. JiZ. LncRNA CARLo-7 facilitates proliferation, migration, invasion, and EMT of bladder cancer cells by regulating Wnt/β-catenin and JAK2/STAT3 signaling pathways.Transl. Androl. Urol.20209542251226110.21037/tau‑20‑1293
     [Google Scholar]
/content/journals/acamc/10.2174/0118715206304668240729093158
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Cyclanoline Reverses Cisplatin Resistance in Bladder Cancer Cells by Inhibiting the JAK2/STAT3 Pathway
Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents) 24, 1360 (2024); https://doi.org/10.2174/0118715206304668240729093158
/content/journals/acamc/10.2174/0118715206304668240729093158
/content/journals/acamc/10.2174/0118715206304668240729093158
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  • Article Type:     Research Article
Keyword(s): Bladder cancer; cisplatin resistance; cyclanoline; HE staining; JAK2/STAT3; tumor transplantation

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