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@# Objective: To explore the effect of interfering insulin-like growth factors-1 receptors (IGF-1R) by small interfering RNA (siRNA) on cell cycle and apoptosis of hypoxic hepatocellular carcinoma HepG2 cells. Methods: The hypoxic hepatocellular carcinoma model was established via cobalt chloride treatment. Three siRNAs targeting IGF1R gene and one negative control siRNA were designed and synthesized. They were transfected into hypoxic HepG2 cells, and 24 h later, the transfection efficiency was detected by fluorescent microscopy. The protein expression of IFG-1R was detected with Western blotting (WB) to screen the siRNA with highest transfection efficacy. The selected siRNA was used to transfect hypoxic HepG2 cells. The proliferation of hypoxic HepG2 cells was determined by MTT assay. Cell cycle distribution and apoptosis were analyzed by Flow cytometry. WB was performed to detect the proteinexpressionsofCDK1,CDK2andCaspase-3inHepG2cells. Results: The hypoxic hepatocellular carcinoma model was successfully established. IGF-1R-siRNA-2 showed the most effective interference efficiency and the most significant knockdown of IGF-1R (all P<0.01). The proliferation of HepG2 cells transfected with IGF-1R siRNA-2 was significantly suppressed (P<0.05 or P<0.01), the cell cycle was blocked at G0/G1 phase (P<0.05), and the apoptosis rate was increased up to (25.3±1.3)% P<0.01). In the meanwhile, the expressions of CDK1 and CDK2 were decreased and the expression of Caspase-3 was increased in hypoxic HepG2 cells after IGF-1R knockdown (P<0.05). Conclusion: Interfering IGF-1R by siRNA inhibits the malignant biological behaviors of hypoxic HepG2 cells via regulating cell cycle and apoptosis-related proteins. IGF-1R may be a potential target for the treatment of HCC.
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@#[Abstract] Objective: To investigate the effect of curcumin on angiogenesis in rats with DEN (diethylnitrosamine)-induced HCC (hepatocellular carcinoma) under hypoxia. Methods: Rat HCC was induced by DEN, and its hepatic hypoxia model was established by ligating hepatic artery. The rats with established HCC model were randomly divided into four groups according to digital table method: lipiodol embolization group (group A), lipiodol combined with curcumin embolization group (group B), lipiodol combined with peripheral liver capsule group (group C), lipiodol combined with curcumin and peripheral liver capsule group (group D), with 10 rats in each group. VEGF expression in HCC cells and tissues, microvessel density (MVD), and median survival time (MST) of rats in each group were compared. Results: VEGF protein expression and microvessel density in group B, D were significantly lower than those in A group ( P <0.01), while those in C group had no significant difference compared with group A ( P >0.05). MST in group B, C and D was significantly longer than that in group A ( P <0.05), and the MST in group D was higher than that in group B and C ( P <0.05). Conclusion: Curcumin can inhibit tumor angiogenesis and decrease VEGF expression and MVD in HCC rats under hypoxia, thus further prolong the survival time of the rats.