Hedgehog signaling regulates the survival of gastric cancer cells by regulating the expression of Bcl-2.
Gastric cancer is the second most common cause of cancer deaths worldwide. The underlying molecular mechanisms of its carcinogenesis are relatively poorly characterized. Hedgehog (Hh) signaling, which is critical for development of various organs including the gastrointestinal tract, has been associated with gastric cancer. The present study was undertaken to reveal the underlying mechanism by which Hh signaling controls gastric cancer cell proliferation. Treatment of gastric cancer cells with cyclopamine, a specific inhibitor of Hh signaling pathway, reduced proliferation and induced apoptosis of gastric cancer cells. Cyclopamine treatment induced cytochrome c release from mitochondria and cleavage of caspase 9. Moreover, Bcl-2 expression was significantly reduced by cyclopamine treatment. These results suggest that Hh signaling regulates the survival of gastric cancer cells by regulating the expression of Bcl-2.
Han
Myoung-Eun
ME
Department of Anatomy, School of Medicine, Pusan National University, Korea.|Medical Research Center for Ischemic Tissue Regeneration, Pusan National University, Beomeo-Ri, Mulgeum-Eup, Yangsan, 626-770, Korea.
Lee
Young-Suk
YS
Department of Anatomy, School of Medicine, Pusan National University, Korea.
Baek
Sun-Yong
SY
Department of Anatomy, School of Medicine, Pusan National University, Korea.
Kim
Bong-Seon
BS
Department of Anatomy, School of Medicine, Pusan National University, Korea.
Kim
Jae-Bong
JB
Department of Anatomy, School of Medicine, Pusan National University, Korea.
Oh
Sae-Ock
SO
Department of Anatomy, School of Medicine, Pusan National University, Korea.|Medical Research Center for Ischemic Tissue Regeneration, Pusan National University, Beomeo-Ri, Mulgeum-Eup, Yangsan, 626-770, Korea.
D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism*; D014704:Veratrum Alkaloids / Q000494:pharmacology
D053823:Hedgehog Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014704:Veratrum Alkaloids; C000541:cyclopamine