Identification of Fangjihuangqi Decoction as a late-stage autophagy inhibitor with an adjuvant anti-tumor effect against non-small cell lung cancer

Chinese Medicine

Research

Yanjun Jiang¹  Junbo Jiang²  Mengyi zheng²  Zhen zhang³  Anqi Li³  Xiaoyi Liu⁴  Yue Song⁵  Qiugu Chen⁵  Jiangyong Gu⁵  Yuan Liao⁵  Jianyong Xiao⁵  Yuhui Tan⁵  Shan Hu⁶  Kun Wang⁶  Tingxiu Zhao⁶  Yujiao Liu⁶  Hua Yi⁶  Xiaoyi Chen⁷ 

[1] Department of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, 999077, Hong Kong, SAR, China;Department of Medical Biotechnology, Guangzhou University of Chinese Medicine, 510006, Guangzhou, China;Department of Pathology and Pathophysiology, Guangzhou University of Chinese Medicine, 510006, Guangzhou, China;Research Center of Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, 510006, Guangzhou, China;Research Center of Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, 510006, Guangzhou, China;Department of Medical Biotechnology, Guangzhou University of Chinese Medicine, 510006, Guangzhou, China;Research Center of Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, 510006, Guangzhou, China;Department of Pathology and Pathophysiology, Guangzhou University of Chinese Medicine, 510006, Guangzhou, China;The Second Clinical College, Guangzhou University of Chinese Medicine, 510006, Guangzhou, China;

关键词: Fangjihuangqi decoction;    Autophagy inhibition;    Sensitization;    Cisplatin;    Paclitaxel;   

DOI  :  10.1186/s13020-023-00770-4

 received in 2023-02-05, accepted in 2023-05-16,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundClinically, although chemotherapy is one of the most commonly used methods of treating tumors, chemotherapeutic drugs can induce autophagic flux and increase tumor cell resistance, leading to drug tolerance. Therefore, theoretically, inhibiting autophagy may improve the efficacy of chemotherapy. The discovery of autophagy regulators and their potential application as adjuvant anti-cancer drugs is of substantial importance. In this study, we clarified that Fangjihuangqi Decoction (FJHQ, traditional Chinese medicine) is an autophagy inhibitor, which can synergistically enhance the effect of cisplatin and paclitaxel on non-small cell lung cancer (NSCLC) cells.MethodsWe observed the changes of autophagy level in NSCLC cells under the effect of FJHQ, and verified the level of the autophagy marker protein and cathepsin. Apoptosis was detected after the combination of FJHQ with cisplatin or paclitaxel, and NAC (ROS scavenger) was further used to verify the activation of ROS-MAPK pathway by FJHQ.ResultsWe observed that FJHQ induced autophagosomes in NSCLC cells and increased the levels of P62 and LC3-II protein expression in a concentration- and time-gradient-dependent manner, indicating that autophagic flux was inhibited. Co-localization experiments further showed that while FJHQ did not inhibit autophagosome and lysosome fusion, it affected the maturation of cathepsin and thus inhibited the autophagic pathway. Finally, we found that the combination of FJHQ with cisplatin or paclitaxel increased the apoptosis rate of NSCLC cells, due to increased ROS accumulation and further activation of the ROS-MAPK pathway. This synergistic effect could be reversed by NAC.ConclusionCollectively, these results demonstrate that FJHQ is a novel late-stage autophagy inhibitor that can amplify the anti-tumor effect of cisplatin and paclitaxel against NSCLC cells.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

41116_2023_37_Article_IEq13.gif

41116_2023_37_Article_IEq1.gif

Fig. 6

Fig. 6

Fig. 5

Fig. 4

Fig. 9

Fig. 3