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

BACKGROUND

Esophageal squamous cell carcinoma(ESCC) often develops resistance to standard chemotherapy regimens of docetaxel/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 of various 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 stress response. This may provide a potential rationale for repurposing CCBs as adjuvant agents in chemotherapy of ESCC.