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Updated: Jun 17, 2025

Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
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Cyclanoline Reverses Cisplatin Resistance in Bladder Cancer Cells by Inhibiting the JAK2/STAT3 Pathway

Linjin Li1, Chengpeng Li1, Feilong Miao1

  • 1Department of Urology, The Third Clinical Institute Affiliated to Wenzhou Medical University, The Third Affiliated Hospital of Shanghai University, Wenzhou People's Hospital, 325099, Wenzhou, China.

Anti-Cancer Agents in Medicinal Chemistry
|August 12, 2024
PubMed
Abstract

Insights

Cyclanoline (Cyc) reverses cisplatin resistance in bladder cancer by inhibiting JAK/STAT3 signaling. This combination therapy shows promise for enhancing cisplatin efficacy in treating bladder cancer patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Cisplatin is a primary treatment for bladder cancer.
  • Cisplatin resistance is a major clinical obstacle.
  • Novel strategies are needed to overcome resistance.

Purpose of the Study:

  • Investigate cyclanoline (Cyc) as a means to overcome cisplatin resistance in bladder cancer.
  • Elucidate the underlying mechanisms of Cyc's action.

Main Methods:

  • Established cisplatin-resistant bladder cancer cell lines (T24/DR, BIU-87/DR).
  • Assessed STAT3, JAK2, and JAK3 phosphorylation using Western Blot.
  • Evaluated cell viability, proliferation, invasion, migration, apoptosis, and cell cycle.
  • Conducted in vivo studies using tumor xenograft models in nude mice.

Main Results:

  • Cisplatin-resistant cells showed elevated STAT3, JAK2, and JAK3 phosphorylation.
  • Cyc treatment, alone or with cisplatin, reduced p-STAT3, inhibited invasion/migration, and induced apoptosis and G0/G1 cell cycle arrest.
  • In vivo studies demonstrated significant tumor growth suppression and cell death.
  • Combination therapy yielded more pronounced effects.

Conclusions:

  • Cyclanoline effectively reverses cisplatin resistance in bladder cancer.
  • The mechanism involves the inhibition of the JAK/STAT3 signaling pathway.
  • Cyc presents a potential therapeutic strategy to improve cisplatin treatment outcomes.
Keywords:
Bladder cancerHE staining.JAK2/STAT3cisplatin resistancecyclanolinetumor transplantation

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