Anhui Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
Eur Rev Med Pharmacol Sci. 2021 Feb;25(4):1869-1880. doi: 10.26355/eurrev_202102_25082.
This study aimed to investigate the reversal effect of verapamil (VER) on the chemoresistance to cisplatin of esophageal squamous cell carcinoma (ESCC) cells.
The reversal effect of VER on cisplatin resistance in ESCC cells was evaluated via CCK-8 assay, colony formation assessment, and flow cytometry. The key genes that mediate this effect were screened via high-throughput transcriptome se¬quencing. The mRNA and protein expression levels of potassium calcium-activated channel subfamily M alpha 1 (KCNMA1) in ESCC cells were examined via quantitative real-time PCR and Western blot analysis, respectively. The protein expressions of KCNMA1 in tissue samples from patients with either positive or negative responses to the therapeutic regimen of VER were determined via immunohistochemistry assay. Cell models with KCNMA1 knockdown and overexpression were es¬tablished to examine the role of KCNMA1 in mediating the reversal effect of VER on the chemoresistance to cisplatin of ESCC cells.
Results revealed that VER significantly decreased the 50% inhibitory concentration of cisplatin, inhibited colony formation, and induced apoptosis in ESCC cells. The curative effects of VER combined with chemotherapeutic drugs in KCNMA1-positive patients were better than those in KCNMA1-negative patients. KCNMA1 upregulation enhanced the reversal effect of VER on the chemoresistance to cisplatin of ESCC cells.
KCNMA1 facilitated the reversal effect of VER on cisplatin resistance in ESCC cells.
本研究旨在探讨维拉帕米（VER）对食管鳞癌（ESCC）细胞顺铂耐药性的逆转作用。
通过 CCK-8 assay、集落形成实验和流式细胞术评估 VER 对 ESCC 细胞顺铂耐药性的逆转作用。通过高通量转录组测序筛选介导这种作用的关键基因。通过定量实时 PCR 和 Western blot 分析分别检测 ESCC 细胞中钾钙激活通道亚家族 M alpha 1（KCNMA1）的 mRNA 和蛋白表达水平。通过免疫组织化学分析测定对 VER 治疗方案有阳性或阴性反应的患者组织样本中 KCNMA1 的蛋白表达。建立 KCNMA1 敲低和过表达的细胞模型，以研究 KCNMA1 在介导 VER 对 ESCC 细胞顺铂耐药性的逆转作用中的作用。
结果表明，VER 显著降低了 ESCC 细胞中顺铂的 50%抑制浓度，抑制了集落形成，并诱导了细胞凋亡。在 KCNMA1 阳性患者中，VER 联合化疗药物的疗效优于 KCNMA1 阴性患者。KCNMA1 的上调增强了 VER 对 ESCC 细胞顺铂耐药性的逆转作用。
KCNMA1 促进了 VER 对 ESCC 细胞顺铂耐药性的逆转作用。
