Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao Shandong, China.
Central Laboratory, The Affiliated Hospital of Qingdao University, Qingdao Shandong, China.
Biochem Biophys Res Commun. 2021 Feb 12;540:108-115. doi: 10.1016/j.bbrc.2021.01.006. Epub 2021 Jan 18.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has the ability to selectively trigger cancer cell apoptosis and can be used as a target for tumor therapy. However, gastric cancer cells are usually insensitive to TRAIL so reducing this drug resistance may improve the treatment of gastric cancer. In this study, we used Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) experiments to determine the effects of 5-fluorouracil (5-FU) and TRAIL on the proliferation of gastric cancer cells. An Annexin V/propidium iodide (PI) staining experiment was used to detect apoptosis, and Western blotting was used to analyze the expression levels of apoptosis-related proteins and mitogen-activated protein kinase (MAPK) pathway proteins. The antitumor effects of 5-FU and TRAIL were verified in vivo using a nude mouse tumorigenesis experiment, and a TUNEL assay was performed to evaluate apoptosis in tumor tissue from the nude mice. We found the combination of 5-FU and TRAIL had a greater inhibitory effect on the proliferation of gastric cancer cells than 5-FU or TRAIL alone both in vivo and in vitro. 5-FU enhanced TRAIL-induced gastric cancer cell apoptosis by inactivating the MAPK pathway. Overall, our analysis firstly provided new insights into the role of 5-FU in increasing sensitivity to TRAIL. 5-FU can be used as a sensitizer for TRAIL, and its administration is a potential strategy for the treatment of gastric cancer.
肿瘤坏死因子相关凋亡诱导配体（TRAIL）具有选择性触发癌细胞凋亡的能力，可作为肿瘤治疗的靶点。然而，胃癌细胞通常对 TRAIL 不敏感，因此降低这种药物耐药性可能会改善胃癌的治疗效果。在这项研究中，我们使用细胞计数试剂盒-8（CCK-8）和 5-乙炔基-2'-脱氧尿苷（EdU）实验来确定 5-氟尿嘧啶（5-FU）和 TRAIL 对胃癌细胞增殖的影响。使用 Annexin V/碘化丙啶（PI）染色实验来检测细胞凋亡，并用 Western blot 分析凋亡相关蛋白和丝裂原活化蛋白激酶（MAPK）通路蛋白的表达水平。使用裸鼠肿瘤发生实验验证了 5-FU 和 TRAIL 的抗肿瘤作用，并通过 TUNEL assay 评估了裸鼠肿瘤组织中的细胞凋亡。我们发现，5-FU 和 TRAIL 联合应用对胃癌细胞的增殖抑制作用大于单独应用 5-FU 或 TRAIL，无论是在体内还是体外。5-FU 通过使 MAPK 通路失活增强了 TRAIL 诱导的胃癌细胞凋亡。总之，我们的分析首先提供了新的见解，即 5-FU 在增加 TRAIL 敏感性方面的作用。5-FU 可用作 TRAIL 的增敏剂，其给药可能是治疗胃癌的一种潜在策略。
