Traditional Chinese Medicine Xiaoai Jiedu Recipe Suppresses the Development of Hepatocellular Carcinoma via Regulating the microRNA-29a/Signal Transducer and Activator of Transcription 3 Axis

Yanfen Shi; Wuming Kong; Yanxu Lu; Yu Zheng

doi:10.2147/OTT.S248797

Traditional Chinese Medicine Xiaoai Jiedu Recipe Suppresses the Development of Hepatocellular Carcinoma via Regulating the microRNA-29a/Signal Transducer and Activator of Transcription 3 Axis

Onco Targets Ther. 2020 Jul 29:13:7329-7342. doi: 10.2147/OTT.S248797. eCollection 2020.

Authors

Yanfen Shi¹, Wuming Kong², Yanxu Lu¹, Yu Zheng³

Affiliations

¹ Department of Traditional Chinese Medicine, The People's Hospital of Jiaozuo City, Jiaozuo City, Henan Province 454000, People's Republic of China.
² Department of Gastroenterology, Shanghai University of Medicine & Health Sciences Affiliated Sixth People's East-Hospital, Shanghai City 201306, People's Republic of China.
³ Department of Spleen and Stomach Disease, Kunming Municipal Hospital of Traditional Chinese Medicine, Kunming City, Yunnan, Province 650051, People's Republic of China.

Abstract

Objective: Hepatocellular carcinoma (HCC) is one of the most frequent and lethal tumors affecting human health worldwide. The aim of this study was to investigate the anti-cancer effects of Xiaoai Jiedu Recipe (XJR) on HCC development and its underlying mechanisms.

Methods: The expression of microRNA-29a (miR-29a) and signal transducer and activator of transcription 3 (STAT3) in HCC tissues and cells was determined by quantitative real-time polymerase chain reaction. The proliferation, migration, and invasion of HCC cells were measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, wound-healing, and transwell assays, respectively. The regulatory relationship between miR-29a and STAT3 in HCC was predicted by TargetScan and analyzed by luciferase reporter and RNA pull-down assays. The protein expression of matrix metalloproteinase (MMP)-2/9 and STAT3 was detected by Western blotting. A xenograft tumor mouse model was established, and tumor weight and volume were measured.

Results: The expression of miR-29a was significantly decreased in HCC tissues and cells compared with that in normal tissues and cells. The up-regulation of miR-29a was related with lymph node metastasis and tumor node metastasis stage. XJR treatment significantly increased the expression of miR-29a, decreased cell viability, migration, and invasion, and reduced the protein expression of MMP-2/9 in HCC cells in a concentration-dependent manner. The anti-tumor effect of XJR on HCC cells was reversed by treatment with miR-29a inhibitor. STAT3 was predicted as a target of miR-29a, and its expression was negatively regulated by miR-29a. Moreover, STAT3 knockdown suppressed the malignant behavior of HCC cells, and its anti-tumor function was reversed by treatment with miR-29a inhibitor. Furthermore, XJR treatment inhibited tumor growth in mice through elevating miR-29a expression and inhibiting STAT3 expression.

Conclusion: XJR suppressed the development of HCC via regulating miR-29a and STAT3.

Keywords: STAT3; Xiaoai Jiedu Recipe; cell behaviors; hepatocellular carcinoma; microRNA-29a.