Abstract
Vinpocetine exerts pharmacological effects against cardiovascular diseases, while few studies focused on its roles in cancer. The present study investigated the roles of vinpocetine in non-small cell lung cancer (NSCLC) and its relationship with cisplatin resistance. A549 cisplatin-resistant cells (A549/DDP) and nuclear factor erythroid 2-related factor 2 (Nrf2)-overexpressing cell lines were established. 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay was conducted to determine cell viability. Annexin V-propidium iodide assay was conducted to determine cell apoptosis. RT-quantitative PCR and western blot analysis were conducted to determine the levels of mRNA and protein, respectively. NSCLC cell tumor-bearing model was constructed to determine the effects of vinpocetine on tumor growth. Treatment with vinpocetine inhibited cell proliferation and promoted cisplatin-induced cell apoptosis. In addition, treatment with vinpocetine suppressed protein expression of Nrf2 and inhibited messenger RNA levels of heme oxygenase 1 and NAD(P)H dehydrogenase quinone 1 induced by cisplatin. Interestingly, the overexpression of Nrf2 abolished the antiproliferative effects of vinpocetine on NSCLC cells. In vivo data suggested that vinpocetine (50 mg/kg) inhibited tumor growth and enhanced the antitumor effects of cisplatin in the NSCLC cell tumor-bearing model. Vinpocetine enhances cisplatin sensitivity of NSCLC cells in part by suppressing Nrf2 signaling.
Footnotes
Contributors Data curation, analysis: QZ, YHu, YHo, WZ, KZ; drafting of the manuscript: QZ, YHu, YHo, WZ, KZ, ZH; concept, design of the study: QZ, ZH. guarantor: ZH. All authors approved the publication of the manuscript.
Funding This research was supported by the Natural Science Foundation of Fujian (2018J01274).
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement
Data are available on reasonable request.
Log in using your username and password
Log in through your institution
PURCHASE SHORT TERM ACCESS
Pay Per Article - You may access this article (from the computer you are currently using) for 1 day for US$37.00
Regain Access - You can regain access to a recent Pay per Article purchase if your access period has not yet expired.