Open Access

Polydatin, a potential NOX5 agonist, synergistically enhances antitumor activity of cisplatin by stimulating oxidative stress in non‑small cell lung cancer

  • Authors:
    • Siyuan Wu
    • Qi Zhao
    • Shengjuan Liu
    • Jiayang Kuang
    • Ji Zhang
    • Annabeth Onga
    • Yiwei Shen
    • Jiaying Wang
    • Hehuan Sui
    • Lianli Ni
    • Yuxin Ye
    • Xinyue Tu
    • Han-Bo Le
    • Yihu Zheng
    • Ri Cui
    • Wangyu Zhu
  • View Affiliations

  • Published online on: June 14, 2024     https://doi.org/10.3892/ijo.2024.5665
  • Article Number: 77
  • Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Non‑small cell lung cancer (NSCLC) is one of the major causes of cancer‑related death worldwide. Cisplatin is a front‑line chemotherapeutic agent in NSCLC. Nevertheless, subsequent harsh side effects and drug resistance limit its further clinical application. Polydatin (PD) induces apoptosis in various cancer cells by generating reactive oxygen species (ROS). However, underlying molecular mechanisms of PD and its effects on cisplatin‑mediated antitumor activity in NSCLC remains unknown. MTT, colony formation, wound healing analyses and flow cytometry was employed to investigate the cell phenotypic changes and ROS generation. Relative gene and protein expressions were evaluated by reverse transcription‑quantitative PCR and western blot analyses. The antitumor effects of PD, cisplatin and their combination were evaluated by mouse xenograft model. In the present study, it was found that PD in combination with cisplatin synergistically enhances the antitumor activity in NSCLC by stimulating ROS‑mediated endoplasmic reticulum stress, and the C‑Jun‑amino‑terminal kinase and p38 mitogen‑activated protein kinase signaling pathways. PD treatment elevated ROS generation by promoting expression of NADPH oxidase 5 (NOX5), and NOX5 knockdown attenuated ROS‑mediated cytotoxicity of PD in NSCLC cells. Mice xenograft model further confirmed the synergistic antitumor efficacy of combined therapy with PD and cisplatin. The present study exhibited a superior therapeutic strategy for some patients with NSCLC by combining PD and cisplatin.
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August-2024
Volume 65 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Wu S, Zhao Q, Liu S, Kuang J, Zhang J, Onga A, Shen Y, Wang J, Sui H, Ni L, Ni L, et al: Polydatin, a potential NOX5 agonist, synergistically enhances antitumor activity of cisplatin by stimulating oxidative stress in non‑small cell lung cancer. Int J Oncol 65: 77, 2024
APA
Wu, S., Zhao, Q., Liu, S., Kuang, J., Zhang, J., Onga, A. ... Zhu, W. (2024). Polydatin, a potential NOX5 agonist, synergistically enhances antitumor activity of cisplatin by stimulating oxidative stress in non‑small cell lung cancer. International Journal of Oncology, 65, 77. https://doi.org/10.3892/ijo.2024.5665
MLA
Wu, S., Zhao, Q., Liu, S., Kuang, J., Zhang, J., Onga, A., Shen, Y., Wang, J., Sui, H., Ni, L., Ye, Y., Tu, X., Le, H., Zheng, Y., Cui, R., Zhu, W."Polydatin, a potential NOX5 agonist, synergistically enhances antitumor activity of cisplatin by stimulating oxidative stress in non‑small cell lung cancer". International Journal of Oncology 65.2 (2024): 77.
Chicago
Wu, S., Zhao, Q., Liu, S., Kuang, J., Zhang, J., Onga, A., Shen, Y., Wang, J., Sui, H., Ni, L., Ye, Y., Tu, X., Le, H., Zheng, Y., Cui, R., Zhu, W."Polydatin, a potential NOX5 agonist, synergistically enhances antitumor activity of cisplatin by stimulating oxidative stress in non‑small cell lung cancer". International Journal of Oncology 65, no. 2 (2024): 77. https://doi.org/10.3892/ijo.2024.5665