Apoptosis of human colorectal carcinoma cells is induced by blocking hepatoma-derived growth factor.
Hepatoma-derived growth factor (HDGF) is a novel multifunctional growth factor that elicits pleiotropic effects on biological processes such as lung remodeling and renal development. Recent studies demonstrated that HDGF is related to tumor proliferation, invasion, angiogenesis, and apoptosis. However, the molecular mechanism of HDGF's involvement in apoptosis remains to be clarified. In this study, we first analyze the role of HDGF in colorectal carcinoma (CRC) progression by immunohistochemistry. Then we used small interference RNA (HDGF-siRNA) to block HDGF and assessed its effect on inducing apoptosis of CRC loVo cells. Apoptosis was detected using flow cytometry (FCM), DNA ladder analysis, and Hoechst 33258 staining. In addition, the expression levels of some apoptosis-related proteins were examined by western blot. The result showed that HDGF expression gradually increased in the colorectal carcinogenesis process. Further studies demonstrated that knock-down of HDGF can down-regulate the survivin, activate the mitochondrial pathway, and induce apoptosis in loVo cells. These findings suggest that HDGF is involved in colorectal carcinogenesis process. Further blocking HDGF exhibits potent pro-apoptotic properties in colon cancer cells. Thus, HDGF might be a potential therapeutic target for human colorectal cancer. These findings may have major implications in the treatment of colorectal cancer.
Liao
Fei
F
Department of Gastroenterology, Renmin Hospital, and Pathology Department, Wuhan University, 99# Zhi yang Road, 430060, Wuhan, Hubei, People's Republic of China.
Dong
Weiguo
W
Fan
Lifang
L
D000236:Adenoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D003092:Colitis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045304:Cytochromes c / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011230:Precancerous Conditions / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics*; D012007:Rectum / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C051610:hepatoma-derived growth factor; D045304:Cytochromes c