Guo Chen,1,* Ya Zhang,2,* Yaqiao Zhou,3 Hao Luo,3 Hongzhi Guan,3 Baiping An4 

1Department of Infectious Diseases, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China; 2Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China; 3Department of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China; 4Department of Oncology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Baiping An, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China, Email anbaiping@cdutcm.edu.cn

Abstract: Despite advancements in cancer treatment through surgery and drugs, hepatocellular carcinoma (HCC) remains a significant challenge, as reflected by its low survival rates. The mammalian target of rapamycin (mTOR) signaling pathway plays a crucial role in regulating the cell cycle, proliferation, apoptosis, and metabolism. Notably, dysregulation leading to the activation of the mTOR signaling pathway is common in HCC, making it a key focus for in-depth research and a target for current therapeutic strategies. This review focuses on the role of the mTOR signaling pathway and its downstream effectors in regulating HCC cell proliferation, apoptosis, autophagy, cell cycle, and metabolic reprogramming. Moreover, it emphasizes the potential of natural products as modulators of the mTOR signaling pathway. When incorporated into combination therapies, these natural products have been demonstrated to augment therapeutic efficacy and surmount drug resistance. These products target key signaling pathways such as mTOR signaling pathways. Examples include 11-epi-sinulariolide acetate, matrine, and asparagus polysaccharide. Their inhibitory effects on these processes suggest valuable directions for the development of more effective HCC therapeutic strategies. Various natural products have demonstrated the ability to inhibit mTOR signaling pathway and suppress HCC progression. These phytochemicals, functioning as mTOR signaling pathway inhibitors, hold great promise as potential anti-HCC agents, especially in the context of overcoming chemoresistance and enhancing the outcomes of combination therapies.

Keywords: hepatocellular carcinoma, natural products, mTOR signaling pathway