IGF-I receptor as an emerging potential molecular-targeted for hepatocellular carcinoma in vitro and in vivo.
Abnormal expression of insulin-like growth factor I receptor (IGF-IR) is associated with hepatocellular carcinoma (HCC) progression with largely unknown mechanisms. In this study, IGF-IR expression among different HCC cell lines and silencing its gene transcription on effects of HCC were investigated by short hairpin RNA (shRNA). Specific shRNA was successfully transfected into Bel-7404 or PLC/PRF/5 cells with 90 or 71 % efficiency. The inhibiting rate of IGF-IR at mRNA level were 54.9 % in Bel-7404 or 59.6 % in PLC/PRF/5 cells in accordance with its protein suppression, with the cell cycles at the G1phase arrest and decreasing cyclinD1 via promoting apoptosis in vitro. With the xenograft models of PLC/PRF/5 cells inserted specific shRNA in vivo, the tumor-forming time (14.0 ± 1.1 days) or tumor volume (143 ± 24 mm3) in the shRNA group was significantly lengthened or smaller than those in the control group (7.2 ± 0.8 days or 372 ± 46 mm3, P < 0.001) or in the neg-shRNA group (7.5 ± 1.0 days or 350 ± 50 mm3, P < 0.001). Silencing the IGF-IR gene transcription inhibited cell proliferation or xenograft tumor growth of HCC, suggesting that IGF-IR might be a novel potential target for HCC gene therapy.
Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, 20 West Temple Road, Nantong, 226001, China.|Medical School of Nantong University, Nantong, 226001, China.
Min
M
Yao
Medical School of Nantong University, Nantong, 226001, China.
Li
L
Wang
Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, 20 West Temple Road, Nantong, 226001, China.
Junling
J
Yang
Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, 20 West Temple Road, Nantong, 226001, China.
Xiaodi
X
Yan
Department of Oncology, Affiliated Hospital of Nantong University, Nantong, 226001, China.
Yin
Y
Cai
Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, 20 West Temple Road, Nantong, 226001, China. yaodf@ahnmc.com.
Dengfu
D
Yao
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D047368:Tumor Burden; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D012333:RNA, Messenger; D034741:RNA, Small Interfering; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1
Cell proliferation; Gene amplification; Gene therapy; Hepatocellular carcinoma; Insulin-like growth factor I receptor; Molecular-targeted; Xenograft tumor