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 G(1) phase 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 mm(3)) in the shRNA group was significantly lengthened or smaller than those in the control group (7.2 +/- 0.8 days or 372 +/- 46 mm(3), P < 0.001) or in the neg-shRNA group (7.5 +/- 1.0 days or 350 +/- 50 mm(3), 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.