Background <p>Esophageal squamous cell carcinoma(ESCC) often develops resistance to standard chemotherapy regimens ofdocetaxel/cisplatin/5-fluorouracil(DCF) therapy. Strategies to overcome chemoresistance remain a significant clinical challenge.</p> Methods <p>DCF-resistant ESCC cell lines were established in the beginning through long-term exposure to chemotherapeutic agents.Gene expression profiles were analyzed via RNA sequencing, and functional assays were conducted to evaluate the impact ofvarious calcium channel blockers(CCBs) on cell viability.</p> Results <p>Transcriptomic analysis revealed enrichment of endoplasmic reticulum(ER) stress pathways in DCF-resistant ESCC cells.Among CCBs tested, combined therapy DCF with CCBs restored chemosensitivity.</p> Conclusion <p>DCF-resistant ESCC cells were resensitized with combined therapy with DCF and CCBs by enhacing ER stressresponse. This may provide a potential rationale for repurposing CCBs as adjuvant agents in chemotherapy of ESCC.</p>

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DCF-resistant ESCC redevelops drug sensitivity when combined with calcium channel blockers due to ER stress response

  • Wenjie Liao,
  • Satoru Matsuda,
  • Tetsuya Takimoto,
  • Kazumasa Fukuda,
  • Masashi Takeuchi,
  • Hirofumi Kawakubo,
  • Hideyuki Saya,
  • Yuko Kitagawa

摘要

Background

Esophageal squamous cell carcinoma(ESCC) often develops resistance to standard chemotherapy regimens ofdocetaxel/cisplatin/5-fluorouracil(DCF) therapy. Strategies to overcome chemoresistance remain a significant clinical challenge.

Methods

DCF-resistant ESCC cell lines were established in the beginning through long-term exposure to chemotherapeutic agents.Gene expression profiles were analyzed via RNA sequencing, and functional assays were conducted to evaluate the impact ofvarious calcium channel blockers(CCBs) on cell viability.

Results

Transcriptomic analysis revealed enrichment of endoplasmic reticulum(ER) stress pathways in DCF-resistant ESCC cells.Among CCBs tested, combined therapy DCF with CCBs restored chemosensitivity.

Conclusion

DCF-resistant ESCC cells were resensitized with combined therapy with DCF and CCBs by enhacing ER stressresponse. This may provide a potential rationale for repurposing CCBs as adjuvant agents in chemotherapy of ESCC.