Shi Yanfen, Kong Wuming, Lu Yanxu, Zheng Yu
Department of Traditional Chinese Medicine, The People's Hospital of Jiaozuo City, Jiaozuo City, Henan Province 454000, People's Republic of China.
Department of Gastroenterology, Shanghai University of Medicine & Health Sciences Affiliated Sixth People's East-Hospital, Shanghai City 201306, People's Republic of China.
Onco Targets Ther. 2020 Jul 29;13:7329-7342. doi: 10.2147/OTT.S248797. eCollection 2020.
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.
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.
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.
XJR suppressed the development of HCC via regulating miR-29a and STAT3.
肝细胞癌（HCC）是全球影响人类健康的最常见且致命的肿瘤之一。本研究旨在探讨消癌解毒方（XJR）对HCC发展的抗癌作用及其潜在机制。
采用定量实时聚合酶链反应检测HCC组织和细胞中微小RNA-29a（miR-29a）和信号转导及转录激活因子3（STAT3）的表达。分别通过3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2-H-四氮唑溴盐、伤口愈合和Transwell实验检测HCC细胞的增殖、迁移和侵袭能力。通过TargetScan预测HCC中miR-29a与STAT3的调控关系，并通过荧光素酶报告基因和RNA下拉实验进行分析。采用蛋白质免疫印迹法检测基质金属蛋白酶（MMP）-2/9和STAT3的蛋白表达。建立异种移植瘤小鼠模型，测量肿瘤重量和体积。
与正常组织和细胞相比，miR-29a在HCC组织和细胞中的表达显著降低。miR-29a的上调与淋巴结转移和肿瘤结节转移分期有关。XJR处理以浓度依赖的方式显著增加miR-29a的表达，降低细胞活力、迁移和侵袭能力，并降低HCC细胞中MMP-2/9的蛋白表达。用miR-29a抑制剂处理可逆转XJR对HCC细胞的抗肿瘤作用。STAT3被预测为miR-29a的靶标，其表达受到miR-29a的负调控。此外，STAT3基因敲低可抑制HCC细胞的恶性行为，用miR-29a抑制剂处理可逆转其抗肿瘤功能。此外，XJR处理通过提高miR-29a表达和抑制STAT3表达来抑制小鼠肿瘤生长。
XJR通过调节miR-29a和STAT3抑制HCC的发展。
