Hubei Selenium and Human Health Institute, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei 445000, China.
Department of Oncology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, Hubei 445000, China.
Biomed Res Int. 2019 Aug 19;2019:2486783. doi: 10.1155/2019/2486783. eCollection 2019.
The incidence of gastric cancer is extremely high in China, prompting the development of effective therapeutic strategies. Sodium selenite (SS) affects the proliferation and redifferentiation of gastric cancer cells and the Adriamycin prodrug Ac-Phe-Lys-PABC-ADM (PADM) reduces toxicity in gastric cancer treatment. However, the mechanisms involved therein remain unclear. In this study, nude mice were transplanted with SGC-7901 gastric cancer cells to construct a tumor xenograft model. After administration of SS and PADM, tumor weight and size were reduced. In addition, the levels of alanine aminotransferase, aspartate transaminase, creatinine, and lactate dehydrogenase were decreased, indicating improved hepatic and renal function and inhibited cancer cell metabolism. Furthermore, combined treatment of SS and PADM downregulated the expression of cell cycle-related proteins (cyclin-dependent kinase 4, Ki67, cyclin E, and cyclin D1), elevated that of proapoptosis proteins (Bax, cleaved caspase-3, cleaved caspase-9, and P53), and upregulated that of mitochondrial apoptosis-associated proteins (apoptotic protease activating factor 1 and second mitochondria-derived activator of caspases). In conclusion, combined treatment of SS and PADM effectively promoted apoptosis in gastric cancer xenografts via the mitochondrial apoptosis pathway.
胃癌在中国的发病率极高，促使人们开发出有效的治疗策略。亚硒酸钠（SS）可影响胃癌细胞的增殖和再分化，阿霉素前药 Ac-Phe-Lys-PABC-ADM（PADM）可降低胃癌治疗的毒性。然而，其具体机制尚不清楚。在本研究中，裸鼠被移植 SGC-7901 胃癌细胞以构建肿瘤异种移植模型。给予 SS 和 PADM 后，肿瘤重量和体积减小。此外，丙氨酸氨基转移酶、天冬氨酸氨基转移酶、肌酐和乳酸脱氢酶的水平降低，表明肝肾功能得到改善，癌细胞代谢受到抑制。此外，SS 和 PADM 的联合治疗下调了细胞周期相关蛋白（细胞周期蛋白依赖性激酶 4、Ki67、细胞周期蛋白 E 和细胞周期蛋白 D1）的表达，上调了促凋亡蛋白（Bax、cleaved caspase-3、cleaved caspase-9 和 P53）的表达，上调了线粒体凋亡相关蛋白（凋亡蛋白酶激活因子 1 和第二线粒体衍生的半胱天冬酶激活因子）的表达。综上所述，SS 和 PADM 的联合治疗通过线粒体凋亡途径有效促进了胃癌异种移植中的细胞凋亡。
