Eur Rev Med Pharmacol Sci 2021; 25 (4): 1869-1880

DOI: 10.26355/eurrev_202102_25082

Upregulation of KCNMA1 facilitates the reversal effect of verapamil on the chemoresistance to cisplatin of esophageal squamous cell carcinoma cells

N. Ge, G.-S. Yang, T.-Y. Zhang, N. Chang, Y.-H. Kang, Q. Zhou, P.-S. Fan

Anhui Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China. fanpingsheng@csco.ac.cn


OBJECTIVE: This study aimed to investigate the reversal effect of verapamil (VER) on the chemoresistance to cisplatin of esophageal squamous cell carcinoma (ESCC) cells.

PATIENTS AND METHODS: 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: 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.

CONCLUSIONS: KCNMA1 facilitated the reversal effect of VER on cisplatin resistance in ESCC cells.

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N. Ge, G.-S. Yang, T.-Y. Zhang, N. Chang, Y.-H. Kang, Q. Zhou, P.-S. Fan
Upregulation of KCNMA1 facilitates the reversal effect of verapamil on the chemoresistance to cisplatin of esophageal squamous cell carcinoma cells

Eur Rev Med Pharmacol Sci
Year: 2021
Vol. 25 - N. 4
Pages: 1869-1880
DOI: 10.26355/eurrev_202102_25082