Abstract: 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 integrinβ6. 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.
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Mao, Z.-J.; Tang, Q.-J.; Zhang, C.-A.; Qin, Z.-F.; Pang, B.; Wei, P.-K.; Liu, B.; Chou, Y.-N. Anti-Proliferation and Anti-Invasion Effects of Diosgenin on Gastric Cancer BGC-823 Cells with HIF-1α shRNAs. Int. J. Mol. Sci. 2012, 13, 6521-6533.
Mao Z-J, Tang Q-J, Zhang C-A, Qin Z-F, Pang B, Wei P-K, Liu B, Chou Y-N. Anti-Proliferation and Anti-Invasion Effects of Diosgenin on Gastric Cancer BGC-823 Cells with HIF-1α shRNAs. International Journal of Molecular Sciences. 2012; 13(5):6521-6533.
Mao, Zhu-Jun; Tang, Qian-Jue; Zhang, Ci-An; Qin, Zhi-Feng; Pang, Bin; Wei, Pin-kang; Liu, Bo; Chou, Yuan-Neng. 2012. "Anti-Proliferation and Anti-Invasion Effects of Diosgenin on Gastric Cancer BGC-823 Cells with HIF-1α shRNAs." Int. J. Mol. Sci. 13, no. 5: 6521-6533.