Gong Hongyan, Cheng Weicai, Wang Yong
Department of General Surgery, Yantaishan Hospital, Yantai, Shandong 264000, P.R. China.
Exp Ther Med. 2019 Jan;17(1):41-50. doi: 10.3892/etm.2018.6901. Epub 2018 Oct 30.
Colon cancer is one of the most common types of gastrointestinal tumor. Previous studies have demonstrated that tumor necrosis factor-(TNF)-related apoptosis-inducing ligand (TRAIL) reduces the aggressiveness of colon cancer tumors and promotes the apoptosis of colon carcinoma cells. In the present study, the inhibitory effects of TRAIL were investigated and the potential mechanism of TRAIL-mediated apoptosis was explored in colon cancer cells. Reverse transcription-quantitative polymerase chain reaction, western blotting, immunofluorescence, immunohistochemistry, TUNEL and flow cytometry assays were used to analyze the effects of TRAIL on the growth, migration, invasion and apoptosis of colon tumor cells. experiments were performed in mice to analyze the therapeutic effects of TRAIL. The results demonstrated that TRAIL significantly suppressed the growth of colorectal tumor cells in a dose-dependent manner (0.5-2.5 mg/ml) and also promoted colon tumor cell death. The migration and invasion of colon tumor cells were inhibited by the downregulation of fibronectin, Vimentin and E-cadherin. The apoptotic rate revealed that TRAIL (2.0 mg/ml) significantly promoted the apoptosis of colon tumor cells by regulating apoptosis-related gene expression. TRAIL administration promoted the apoptosis of colon tumor cells via the exogenous apoptosis signaling pathway due to the upregulation of caspase-3, caspase-8 and nuclear factor-κB protein expression. assays revealed that TRAIL administration significantly inhibited tumor growth and promoted apoptotic body and lymphocyte infiltration, which led to increased survival in tumor-bearing mice compared with the control group. Immunohistochemistry revealed that P53 and B-cell lymphoma-2 were downregulated in TRAIL-treated tumors. In conclusion, TRAIL treatment significantly inhibited the growth and aggressiveness of colon tumors by inducing apoptosis via the exogenous apoptosis pathway, which suggests that TRAIL may be a potential anticancer agent for colon carcinoma therapy.
结肠癌是最常见的胃肠道肿瘤类型之一。先前的研究表明,肿瘤坏死因子-(TNF)-相关凋亡诱导配体(TRAIL)可降低结肠癌肿瘤的侵袭性,并促进结肠癌细胞的凋亡。在本研究中,研究了TRAIL的抑制作用,并探讨了TRAIL介导的结肠癌细胞凋亡的潜在机制。采用逆转录定量聚合酶链反应、蛋白质印迹法、免疫荧光法、免疫组织化学法、TUNEL法和流式细胞术分析TRAIL对结肠肿瘤细胞生长、迁移、侵袭和凋亡的影响。在小鼠中进行实验以分析TRAIL的治疗效果。结果表明,TRAIL以剂量依赖性方式(0.5 - 2.5mg/ml)显著抑制结直肠肿瘤细胞的生长,并促进结肠肿瘤细胞死亡。纤维连接蛋白、波形蛋白和E-钙黏蛋白的下调抑制了结肠肿瘤细胞的迁移和侵袭。凋亡率显示,TRAIL(2.0mg/ml)通过调节凋亡相关基因表达显著促进结肠肿瘤细胞的凋亡。由于半胱天冬酶-3、半胱天冬酶-8和核因子-κB蛋白表达上调,TRAIL给药通过外源性凋亡信号通路促进结肠肿瘤细胞凋亡。实验表明,TRAIL给药显著抑制肿瘤生长,促进凋亡小体和淋巴细胞浸润,与对照组相比,荷瘤小鼠的生存期延长。免疫组织化学显示,在TRAIL治疗的肿瘤中,P53和B细胞淋巴瘤-2表达下调。总之,TRAIL治疗通过外源性凋亡途径诱导凋亡,显著抑制结肠肿瘤的生长和侵袭性,这表明TRAIL可能是一种潜在的结肠癌治疗抗癌药物。