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• Mao, Z
• Tang, Q
• Zhang, C
• Qin, Z
• Pang, B
• Wei, P
• Liu, B
• Chou, Y
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• Tang, Q
• Zhang, C
• Qin, Z
• Pang, B
• Wei, P
• Liu, B
• Chou, Y
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• Tang, Q
• Zhang, C
• Qin, Z
• Pang, B
• Wei, P
• Liu, B
• Chou, Y

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Int. J. Mol. Sci. 2012, 13(5), 6521-6533; doi:10.3390/ijms13056521

Article

Anti-Proliferation and Anti-Invasion Effects of Diosgenin on Gastric Cancer BGC-823 Cells with HIF-1α shRNAs

Zhu-Jun Mao ¹ , Qian-Jue Tang ¹ , Ci-An Zhang ² , Zhi-Feng Qin ² , Bin Pang ³ , Pin-kang Wei ^2,* , Bo Liu ^4,*  and Yuan-Neng Chou ⁵

¹ Department of Obstetrics and Gynecology, Longhua Hospital Shanghai University of Traditional Chinese medicine, Shanghai 200032, China ² Department of Traditional Chinese medicine, Shanghai Changzheng Hospital, Senond Military Medical University, Shanghai 200003, China ³ Air Force Center of Aviation Medical Evaluation and Training, Dujiangyan 611833, China ⁴ Cardiovascular Department, Shanghai ChangHai Hospital, Second Military Medical University, Shanghai 200003, China ⁵ Shanghai University of Traditional Chinese medicine, Shanghai 201203, China

* Authors to whom correspondence should be addressed.

Received: 22 February 2012; in revised form: 2 April 2012 / Accepted: 9 May 2012 / Published: 24 May 2012

(This article belongs to the Section Bioactives and Nutraceuticals)

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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.

Keywords: gastric cancer; HIF-1α; hypoxia; shRNA; diosgenin

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