TY - JOUR T1 - Vinpocetine enhances cisplatin sensitivity of non-small cell lung cancer cells by reducing the nuclear factor erythroid 2-related factor 2 signaling JF - Journal of Investigative Medicine JO - J Investig Med DO - 10.1136/jim-2022-002369 SP - jim-2022-002369 AU - Qingyang Zhuang AU - Yunjian Huang AU - Yaping Hong AU - Wu Zhuang AU - Kai Zhu AU - Zhangzhou Huang Y1 - 2022/05/16 UR - http://hw-f5-jim.highwire.org/content/early/2022/05/16/jim-2022-002369.abstract N2 - 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.Data are available on reasonable request. ER -