Combination of TrxR1 inhibitor and lenvatinib triggers ROS-dependent cell death in human lung cancer cells

Zheng, Peisen; Xia, Yiqun; Shen, Xin; Lu, Hui; Chen, Yinghua; Xu, Chenxin; Qiu, Chenyu; Zhang, Yafei; Zou, Peng; Cui, Ri; Huang, Xiaoying

doi:10.7150/ijbs.86160

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Int J Biol Sci 2024; 20(1):249-264. doi:10.7150/ijbs.86160 This issue Cite

Research Paper

Combination of TrxR1 inhibitor and lenvatinib triggers ROS-dependent cell death in human lung cancer cells

Peisen Zheng^1,3#, Yiqun Xia^1,2#, Xin Shen^3#, Hui Lu^3#, Yinghua Chen³, Chenxin Xu³, Chenyu Qiu³, Yafei Zhang³, Peng Zou^1,3✉, Ri Cui^1,3✉, Xiaoying Huang^1,2✉

1. Pulmonary Division, Wenzhou Key Laboratory of Interdiscipline and Translational Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou, Zhejiang, China.
2. Wenzhou Key Laboratory of Heart and Lung, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou Medical University, Wenzhou, Zhejiang, China.
3. School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
# These authors contributed equally to the article.

Citation:

Zheng P, Xia Y, Shen X, Lu H, Chen Y, Xu C, Qiu C, Zhang Y, Zou P, Cui R, Huang X. Combination of TrxR1 inhibitor and lenvatinib triggers ROS-dependent cell death in human lung cancer cells. Int J Biol Sci 2024; 20(1):249-264. doi:10.7150/ijbs.86160. https://www.ijbs.com/v20p0249.htm

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Abstract

Lung cancer is one of the most lethal diseases in the world. Although there has been significant progress in the treatment of lung cancer, there is still a lack of effective strategies for advanced cases. Lenvatinib, a multi-targeted tyrosine kinase inhibitor, has achieved much attention due to its antitumor properties. Nevertheless, the use of lenvatinib is restricted by the characteristics of poor efficacy and drug resistance. In this study, we assessed the effectiveness of lenvatinib combined with thioredoxin reductase 1 (TrxR1) inhibitors in human lung cancer cells. Our results indicate that the combination therapy involving TrxR1 inhibitors and lenvatinib exhibited significant synergistic antitumor effects in human lung cancer cells. Moreover, siTrxR1 also showed significant synergy with lenvatinib in lung cancer cells. Mechanically, we demonstrated that ROS accumulation significantly contributes to the synergism between lenvatinib and TrxR1 inhibitor auranofin. Furthermore, the combination of lenvatinib and auranofin can activate endoplasmic reticulum stress and JNK signaling pathways to achieve the goal of killing lung cancer cells. Importantly, combination therapy with lenvatinib and auranofin exerted a synergistic antitumor effect in vivo. To sum up, the combination therapy involving lenvatinib and auranofin may be a potential strategy for treating lung cancer.

Keywords: TrxR1, Lenvatinib, Lung cancer, Auranofin, ROS

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APA

Zheng, P., Xia, Y., Shen, X., Lu, H., Chen, Y., Xu, C., Qiu, C., Zhang, Y., Zou, P., Cui, R., Huang, X. (2024). Combination of TrxR1 inhibitor and lenvatinib triggers ROS-dependent cell death in human lung cancer cells. International Journal of Biological Sciences, 20(1), 249-264. https://doi.org/10.7150/ijbs.86160.

ACS

Zheng, P.; Xia, Y.; Shen, X.; Lu, H.; Chen, Y.; Xu, C.; Qiu, C.; Zhang, Y.; Zou, P.; Cui, R.; Huang, X. Combination of TrxR1 inhibitor and lenvatinib triggers ROS-dependent cell death in human lung cancer cells. Int. J. Biol. Sci. 2024, 20 (1), 249-264. DOI: 10.7150/ijbs.86160.

NLM

CSE

Zheng P, Xia Y, Shen X, Lu H, Chen Y, Xu C, Qiu C, Zhang Y, Zou P, Cui R, Huang X. 2024. Combination of TrxR1 inhibitor and lenvatinib triggers ROS-dependent cell death in human lung cancer cells. Int J Biol Sci. 20(1):249-264.

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