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Azelnidipine inhibits esophageal squamous cell carcinoma proliferation in vivo and in vitro by targeting MEK1/2.


ABSTRACT: Epidemiological and mechanistic studies suggest that some US Food and Drug Administration (FDA)-approved drugs can reduce the incidence of cancer and inhibit tumor growth. Therefore, investigating FDA-approved drugs for cancer chemoprevention is a promising strategy. In this study, we screened FDA-approved drugs and found that azelnidipine, a Ca channel blocker widely used in the treatment of hypertension, inhibits the growth of esophageal squamous cell carcinoma (ESCC) in vitro and in vivo. We identified that MEK1/2 were direct targets of azelnidipine through pull-down assay and cellular thermal shift assay. Azelnidipine could suppress kinase activity of MEK1/2 through in vitro kinase assay. Hypophosphorylation of ERK1/2 decreased the levels of Cyclin D1/CDK6 in ESCC cells after azelnidipine treatment. More importantly, azelnidipine, like trametinib, inhibited the growth of ESCC in vivo. In conclusion, azelnidipine, a novel dual MEK1/2 inhibitor, exerted antitumor effects against ESCC cell lines and patient-derived xenograft in ESCC.

SUBMITTER: Zhao L 

PROVIDER: S-EPMC9574346 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Azelnidipine inhibits esophageal squamous cell carcinoma proliferation <i>in vivo</i> and <i>in vitro</i> by targeting MEK1/2.

Zhao Lili L   Zhang Yuhan Y   Li Ang A   Lu Xuebo X   Li Mingzhu M   Yuan Qiang Q   Yang Ning N   Zhao Xiaokun X   Li Xin X   Jiang Yanan Y   Liu Kangdong K  

Molecular therapy oncolytics 20220926


Epidemiological and mechanistic studies suggest that some US Food and Drug Administration (FDA)-approved drugs can reduce the incidence of cancer and inhibit tumor growth. Therefore, investigating FDA-approved drugs for cancer chemoprevention is a promising strategy. In this study, we screened FDA-approved drugs and found that azelnidipine, a Ca channel blocker widely used in the treatment of hypertension, inhibits the growth of esophageal squamous cell carcinoma (ESCC) <i>in vitro</i> and <i>in  ...[more]

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