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Gene Expression Profiling of Hedgehog Signaling Pathway Inhibition in Human Colon Cancer Cells
Huang Xuan1, Zhang Weilong2, Luo Qintian1, Li Yong1, Zhang Junyan1, Deng Libin2, Lü Nonghua3, Luo Shiwen1*
1Center for Experimental Medicine, the First Affiliated Hospital of Nanchang University, Nanchang 330006, China; 2Institute of Translational Medical, Nanchang University, Nanchang 330006, China; 3Department of Gastroentero
Abstract: Hedgehog signaling pathway plays an important role in animal development and tumorigenesis. In the present study， components of hedgehog signaling pathway were detected in HT-29 cells other than SW-480 or Caco-2 cells by Western blot. Blocking of hedgehog signaling by GANT61， which is a small molecule inhibitor of Gli1/2， can significantly decrease the survival rate and proliferation of colon cancer cells， whereas cyclopamine， the conventional Smo inhibitor， showed only modest cytotoxic activity. Gene expression profiling of hedgehog signaling inhibited HT-29 cells was determinated by cDNA microarray. Results indicated that gene expression was partially blocked and differential expressed genes were primarily knocked-down. Moreover， cyclopamine may be principally involved with cell endogenous stimulus， while GANT61 was related to metabolic and steroid biosynthesis and MAPK signaling pathway. Both of them affect pathways in celluar immunity and cell apoptosis. Our findings suggest that inactivation of hedgehog signaling may be an attractive target for the treatment of colon cancer.
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