TY - JOUR
T1 - DCF-resistant ESCC redevelops drug sensitivity when combined with calcium channel blockers due to ER stress response
AU - Liao, Wenjie
AU - Matsuda, Satoru
AU - Takimoto, Tetsuya
AU - Fukuda, Kazumasa
AU - Takeuchi, Masashi
AU - Kawakubo, Hirofumi
AU - Saya, Hideyuki
AU - Kitagawa, Yuko
N1 - Publisher Copyright:
© The Author(s) under exclusive licence to The Japan Esophageal Society 2025.
PY - 2025/10
Y1 - 2025/10
N2 - 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.
AB - 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.
KW - Calcium channel blockers
KW - Drug evaluation
KW - Drug resistance
KW - Endoplasmic reticulum stress
KW - Esophageal squamous cell carcinoma
UR - https://www.scopus.com/pages/publications/105010476479
UR - https://www.scopus.com/pages/publications/105010476479#tab=citedBy
U2 - 10.1007/s10388-025-01146-3
DO - 10.1007/s10388-025-01146-3
M3 - Article
C2 - 40637990
AN - SCOPUS:105010476479
SN - 1612-9059
VL - 22
SP - 631
EP - 640
JO - Esophagus
JF - Esophagus
IS - 4
ER -