1 Department of Radiology, School of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, China.
2 Department of Pathology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China.
Technol Cancer Res Treat. 2019 Jan-Dec;18:1533033819853290. doi: 10.1177/1533033819853290.
The combination of gene therapy and radiation is a promising new treatment for cancer. This study aimed to clarify the synergistic effect of targeted oncolytic adenovirus (radiotherapy-tumor necrosis factor-related apoptosis-inducing ligand) and radiotherapy on colorectal cancer cells and elucidate the mechanisms of the underlying antitumor activity. Viability, cell cycle status, and apoptosis of treated colorectal cancer cells were determined via MTT and flow cytometric assays. The molecular mechanism underlying apoptotic pathway activation was elucidated through Western blot analysis of caspase-8, caspase-3, and PARP proteins. Combination treatment with radiotherapy-tumor necrosis factor-related apoptosis-inducing ligand and radiotherapy displayed significantly greater antitumor activity than either of the monotherapies. The primary mechanism behind the antitumor activity in the SW480 and Lovo colorectal cancer cell lines was apoptosis induction through the caspase pathway and G1 phase arrest. In an SW480 xenograft model of colorectal cancer, the combination therapy achieved a significantly greater reduction in tumor volume than the monotherapies. Overall, in this study, we demonstrate that the oncolytic radiotherapy-tumor necrosis factor-related apoptosis-inducing ligand construct can sensitize human colorectal cancer cells to radiation-induced apoptosis both in vitro and in vivo. Therefore, our findings point toward a novel synergistic approach to colorectal cancer treatment.
基因治疗与放射疗法相结合是一种有前途的癌症新疗法。本研究旨在阐明靶向溶瘤腺病毒（放射治疗-肿瘤坏死因子相关凋亡诱导配体）与放射疗法对结直肠癌细胞的协同作用，并阐明其抗肿瘤活性的潜在机制。通过 MTT 和流式细胞术检测处理后的结直肠癌细胞的活力、细胞周期状态和凋亡。通过 Western blot 分析半胱天冬酶-8、半胱天冬酶-3 和 PARP 蛋白来阐明凋亡途径激活的分子机制。放射治疗-肿瘤坏死因子相关凋亡诱导配体与放射疗法联合治疗的抗肿瘤活性明显强于单一疗法。在 SW480 和 Lovo 结直肠癌细胞系中，抗肿瘤活性的主要机制是通过半胱天冬酶途径诱导细胞凋亡和 G1 期阻滞。在结直肠癌细胞 SW480 的异种移植模型中，联合治疗组比单一疗法组更显著地降低了肿瘤体积。总的来说，在这项研究中，我们证明了溶瘤放射治疗-肿瘤坏死因子相关凋亡诱导配体构建物可以在体外和体内增强人结直肠癌细胞对放射诱导凋亡的敏感性。因此，我们的研究结果表明了一种治疗结直肠癌的新协同方法。
