Solamargine induces hepatocellular carcinoma cell apoptosis and autophagy via inhibiting LIF/miR-192-5p/CYR61/Akt signaling pathways and eliciting immunostimulatory tumor microenvironment

Journal of Hematology & Oncology

Tao Wang¹  Shuangshuang Yin¹  Haiyang Yu¹  Yuling Qiu²  Wenke Jin³  Leilei Fu³ 

[1] Key Laboratory of Pharmacology of Traditional Chinese Medical Formulae, Ministry of Education, and State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine;School of Pharmacy, Tianjin Medical University;Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs, School of Life Science and Engineering, Southwest Jiaotong University;

关键词: Hepatocellular carcinoma;    Traditional Chinese herb;    Solamargine;    Apoptosis;    Autophagy;    Tumor microenvironment;   

DOI  :  10.1186/s13045-022-01248-w

来源: DOAJ

【 摘 要 】

Abstract Hepatocellular carcinoma (HCC) is well-known to be a highly prevalent malignant tumor, but the treatment of this pathological state has been still challenging. Solamargine (SM), a traditional Chinese herb-derived compound, has been widely reported to possess multiple antitumor properties. However, whether SM plays a vital role in HCC therapy and how it exerts an antitumor effect remains unclear. Thus, in this study, we demonstrated that SM inhibited the proliferation of HCC and effectively induced HCC cell apoptosis and autophagy in vitro and in vivo. Mechanistically, the oncogenic factor LIF was aberrantly elevated in HCC tissues and down-regulated by SM in HCC cells, as well as subsequently the overexpression of LIF could restore the anti-HCC effects of SM via miR-192-5p/CYR61/Akt signaling pathways. Additionally, SM could repolarize tumor associated macrophages by LIF/p-Stat3 to inhibit the growth and epithelial-mesenchymal transition of HCC, and simultaneously affected other immune cell populations in the immune (tumor) microenvironment by regulating macrophages, such as MDSCs, DCs and T cell populations. Together, these findings exploit the potential use of SM against HCC and shed light on exploring SM as a potent candidate drug for the future HCC therapeutics.

【 授权许可】

Unknown