Gracillin Shows Potential Efficacy Against Non-Small Cell Lung Cancer Through Inhibiting the mTOR Pathway

Frontiers in Oncology

Yamei Li¹  Xiaoxuan Liu¹  Mingchun Li²  Hai Liu³  Bang Xiao⁴  Minhong Zhang⁵  Jianqiong Yang⁵  Yaoling Luo⁵ 

[1] College of Pharmacy, Gannan Medical University, Ganzhou, China;Department of Oncology of the First Clinical Medical College, Gannan Medical University, Ganzhou, China;National Engineering Research Center for Modernization of Traditional Chinese Medicine-Hakka Medical Resources Branch, Gannan Medical University, Ganzhou, China;School of Rehabilitation Medicine, Gannan Medical University, Ganzhou, China;The Clinical Medicine Research Center of the First Clinical Medical College, Gannan Medical University, Ganzhou, China;

关键词: gracillin;    non-small cell lung cancer;    autophagy;    mTOR signaling pathway;    anti-tumor;   

DOI  :  10.3389/fonc.2022.851300

来源: DOAJ

【 摘 要 】

The leading cause of cancer deaths is lung cancer, non-small cell lung cancer (NSCLC), the most common type of lung cancers, remains a difficult cancer to treat and cure. It is urgent to develop new products to treat NSCLS. Gracillin, extracted from Reineckia carnea, Dioscorea villosa, and other medicinal plants, has anti-tumor potential with toxic effect on a variety of tumor cells such as NSCLC. However, the anti-NSCLC mechanism of gracillin is not completely clear. In this study, A549 cells and athymic nude mice were used as models to evaluate the anti-NSCLC effects of gracillin. The antiproliferative activity of gracillin on A549 cells was conducted by CCK-8, and obvious autophagy was observed in gracillin-treated A549 through transmission electron microscopy. Furthermore, the expressions of Beclin-1, LC3-II, and WIPI1 were upregulated, while the expression of p62 was downregulated in gracillin-treated A549. The further mechanism study found that the mTOR signaling pathway was significantly inhibited by gracillin. Accordingly, the PI3K/Akt pathway positively regulating mTOR was inhibited, and AMPK negatively regulating mTOR was activated. Meanwhile, LC3-II transformation was found to be significantly reduced after WIPI1 was silenced in A549 cells but increased after gracillin treatment. It also proves that WIPI is involved in the process of gracillin regulating A549 autophagy. At last, the anti-tumor growth activity of gracillin in vivo was validated in A549-bearing athymic nude mice. In conclusion, gracillin has anti-NSCLC activity by inducing autophagy. The mechanism maybe that gracillin inhibited the mTOR signaling pathway. Gracillin has the potential to be a candidate product for the treatment of NSCLC in the future.

【 授权许可】

Unknown