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Vinpocetine enhances cisplatin sensitivity of non-small cell lung cancer cells by reducing the nuclear factor erythroid 2-related factor 2 signaling
  1. Qingyang Zhuang1,
  2. Yunjian Huang2,
  3. Yaping Hong2,
  4. Wu Zhuang2,
  5. Kai Zhu2,
  6. Zhangzhou Huang2
  1. 1Department of Radiation Oncology, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou, Fujian, China
  2. 2Department of Thoracic Oncology, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou, Fujian, China
  1. Correspondence to Zhangzhou Huang, Department of thoracic oncology, Fujian Cancer Hospital & Fujian Medical University cancer Hospital, Fuzhou, Fujian, China; huangzhangzhou{at}fjzlhospital.com

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.

  • lung diseases

Data availability statement

Data are available on reasonable request.

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Data availability statement

Data are available on reasonable request.

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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.