Xue Shouyu, Geng Aimin, Lian Ting, Liu Yun
Clinical Medical School, Xi'an Medical University, Xi'an 710021, Shaanxi Province, China.
Department of Urological Surgery, Chang' an Hospital, Xi'an 710016, Shaanxi Province, China.
Toxicol Res (Camb). 2022 Aug 30;11(5):804-811. doi: 10.1093/toxres/tfac058. eCollection 2022 Oct.
(SB) is a widely used herbal medicine in China, with various pharmacological effects such as anti-oxidation, anti-inflammation, and anti-cancer. This work is aimed to investigate the tumor-suppressive effect of SB in cervical cancer (CC) and to identify its underlying mechanisms.
CC cell lines (HeLa and HT-3) were treated with different concentrations of SB chloroform extract (ECSB) (0, 0.2, 0.5 mg/ml). MiR-195-5p and LOXL2 mRNA expression in CC cell lines and tissue samples was detected by quantitative real-time polymerase chain reaction. Cell counting kit-8 experiment was utilized to examine cell viability; TUNEL assay and Transwell experiment was executed to examine cell apoptosis, migration, and invasion. Western blotting experiments were implemented to detect LOXL2 protein expression. Bioinformatics and dual-luciferase reporter gene experiment were executed to examine the binding relationship between miR-195-5p and LOXL2.
ECSB repressed the viability, migration, and invasion of HeLa and HT-3 cells, and promoted cell apoptosis in a dose-dependent manner. MiR-195-5p was remarkably under-expressed in CC tissues and cells, and ECSB up-regulated miR-195-5p expression. MiR-195-5p inhibitors partially counteracted the suppressive effects of ECSB on the malignant phenotypes of HeLa and HT-3 cells. LOXL2 was a downstream target of miR-195-5p, and ECSB up-modulated LOXL2 expression by specifically repressing miR-195-5p.
SB restrains CC cell proliferation and metastasis and promotes cell apoptosis via miR-195-5p/LOXL2, which may be a potential therapeutic agent for CC treatment.
蛇莓(SB)是中国广泛使用的一种草药,具有抗氧化、抗炎和抗癌等多种药理作用。本研究旨在探讨蛇莓对宫颈癌(CC)的抑瘤作用并确定其潜在机制。
用不同浓度的蛇莓氯仿提取物(ECSB)(0、0.2、0.5mg/ml)处理CC细胞系(HeLa和HT-3)。通过定量实时聚合酶链反应检测CC细胞系和组织样本中miR-195-5p和LOXL2 mRNA的表达。利用细胞计数试剂盒-8实验检测细胞活力;进行TUNEL检测和Transwell实验检测细胞凋亡、迁移和侵袭。通过蛋白质免疫印迹实验检测LOXL2蛋白表达。进行生物信息学和双荧光素酶报告基因实验检测miR-195-5p与LOXL2之间的结合关系。
ECSB抑制HeLa和HT-3细胞的活力、迁移和侵袭,并以剂量依赖的方式促进细胞凋亡。miR-195-5p在CC组织和细胞中显著低表达,ECSB上调miR-195-5p的表达。miR-195-5p抑制剂部分抵消了ECSB对HeLa和HT-3细胞恶性表型的抑制作用。LOXL2是miR-195-5p的下游靶点,ECSB通过特异性抑制miR-195-5p上调LOXL2的表达。
蛇莓通过miR-195-5p/LOXL2抑制CC细胞增殖和转移并促进细胞凋亡,可能是CC治疗的一种潜在治疗药物。