Mao Zhu-Jun, Tang Qian-Jue, Zhang Ci-An, Qin Zhi-Feng, Pang Bin, Wei Pin-Kang, Liu Bo, Chou Yuan-Neng
Department of Obstetrics and Gynecology, Longhua Hospital Shanghai University of Traditional Chinese medicine, Shanghai 200032, China.
Department of Traditional Chinese medicine, Shanghai Changzheng Hospital, Senond Military Medical University, Shanghai 200003, China.
Int J Mol Sci. 2012;13(5):6521-6533. doi: 10.3390/ijms13056521. Epub 2012 May 24.
Drug resistance is a major factor for the limited efficacy of chemotherapy in gastric cancer treatment. Hypoxia-inducible factor-1α (HIF-1α), a central transcriptional factor in hypoxia, is suggested to participate in the resistance. Here, we identified a hypoxia-mimic (cobalt chloride) sensitive gastric cell line BGC-823 to explore whether diosgenin, an aglycone of steroidal saponins, can inhibit cancer cell invasion and survival of solid tumor in a hypoxic mimic microenvironment. We have shown that diosgenin is a potent candidate for decreasing the ability of invasion and survival in cobalt chloride treated BGC-823 cells. In addition, when combined with HIF-1α specific short hairpin RNA (shRNA), diosgenin can inhibit BGC-823 cells more effectively. The anti-invasion role of diosgenin may be related to E-cadherin, integrinα5 and integrin β6. These results suggest that diosgenin may be a useful compound in controlling gastric cancer cells in hypoxia condition, especially when combined with down-regulated HIF-1α.
耐药性是胃癌治疗中化疗疗效有限的主要因素。缺氧诱导因子-1α（HIF-1α）是缺氧状态下的核心转录因子，提示其参与耐药过程。在此，我们鉴定出一种对缺氧模拟物（氯化钴）敏感的胃癌细胞系BGC-823，以探究甾体皂苷元薯蓣皂苷元是否能在缺氧模拟微环境中抑制癌细胞侵袭和实体瘤细胞存活。我们已表明，薯蓣皂苷元是降低经氯化钴处理的BGC-823细胞侵袭和存活能力的有力候选物。此外，当与HIF-1α特异性短发夹RNA（shRNA）联合使用时，薯蓣皂苷元能更有效地抑制BGC-823细胞。薯蓣皂苷元的抗侵袭作用可能与E-钙黏蛋白、整合素α5和整合素β6有关。这些结果表明，薯蓣皂苷元可能是在缺氧条件下控制胃癌细胞的有用化合物，尤其是与下调HIF-1α联合使用时。
