Angiogenesis Of Hepatocellular Carcinoma Cells Research Articles

Over-expression of Thrombospondin 4 correlates with loss of miR-142 and contributes to migration and vascular invasion of advanced hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common malignancy found worldwide and is associated with a high incidence of metastasis and vascular invasion. Elucidating the molecular mechanisms that underlie HCC tumorigenesis and progression is necessary for the development of novel therapeutics. By analyzing the Cancer Genome Atlas Network (TCGA) dataset, we identified Thrombospondin 4 (THBS4) is significantly overexpressed in HCC samples and is correlated with prognosis. Overexpression of THBS4 was also highly correlated with vascular invasion of advanced HCC. While THBS4 is often overexpressed in HCC it has also been shown to inhibit tumor growth by mediating cell-to-cell and cell-to-matrix interactions. Here, we identified that knockdown of THBS4 inhibits migration and invasion of HCC cells and inhibits HCC induced angiogenesis. MiRNAs are crucial regulators of multiple cellular processes, and aberrant expression of miRNAs has been observed to effect cancer development and progression. We further found that miR-142 is an upstream regulator of THBS4 in HCC cells. Moreover, miR-142 was significantly down-regulated in HCC tissue samples and correlated with overexpression of THBS4. Overexpression of miR-142 inhibited invasion and angiogenesis of HCC cells and re-expression of THBS4 overcame these effects of miR-142 expression. Stable over-expression of miR-142 significantly inhibited tumour growth in a xenograft tumour model through inhibiting THBS4 expression and tumor angiogenesis. In conclusion, our findings indicate that loss of miR-142 results in the over-expression of THBS4, which enhances HCC migration and vascular invasion. Thus, targeting THBS4 or miR-142 may provide a promising therapeutic strategy for treatment of advanced HCC.

Effects of Triple Effective RNA (teRNA) on the Inhibition of Hepatocellular Carcinoma Cells.

The occurrence and development of hepatocellular carcinoma (HCC) is a complicate process involved in genetic mutation and epigenetic regulation. Successful HCC therapy needs multi-targets be involved. The aim of this study was to provide a triple effective RNA (teRNA) which composed of the specific siRNAs targeting NET-1 and VEGF and dsRNA activating TLR3, and explored its anti-HCC roles and mechanism. Real-time quantitative PCR (RT-qPCR), Western blot, immunofluorescence staining, MTT, Annexin V-FITC flow cytometry, Transwell and in-vitro Angiogenesis assay were used to measure the cell biological functions and protein expression analysis. Furthermore in in-vivo mouse model, teRNA inhibited tumor growth were detected by immunohistochemistry and TUNEL assay. Results showed that the proliferation, migration and angiogenesis of HCC cells were inhibited by teRNA effectively, the cell apoptosis also was induced, and further tumor growth was suppressed in-vivo. The gene silencing mechanism of teRNA was in an Ago2-dependent manner with no interferon response. The study suggests that NET-1, VEGF and TLR3 might be better targets for HCC treatment and combined these targets in form of a multi-target small RNA, teRNA could be a stagey for the development of anti-HCC drugs.

The effect of HS-111, a novel thiazolamine derivative, on apoptosis and angiogenesis of hepatocellular carcinoma cells

Hepatocellular carcinoma (HCC) is one of the most common malignancies, yet there have been no significant advances in effective therapeutics. In this study, HS-111 was synthesized as a novel thiazolamine derivative, N-(5-(2-chlorobenzyl) thiazole-2-yl) benzofuran-2-carboxamide, and its anticancer effect and mechanism were examined in human HCC cells. HS-111 strongly suppressed the growth of HCC cells in a dose-dependent manner. Also, apoptosis by HS-111 was identified by DAPI and TUNEL staining, and the increases of the cleaved caspase-3 were observed. In addition, HS-111 decreased protein expression of hypoxia-inducible factor (HIF-1α) and secretion of vascular endothelial growth factor (VEGF), and inhibited tube formation and the migration of human umbilical vein endothelial cells (HUVECs). These results showed that HS-111 not only inhibited cell growth and angiogenesis, but also induced apoptosis of human HCC cells. We suggest that HS-111 may be a potential candidate for chemotherapy against HCC.

Effect of preoperative transcatheter arterial chemoembolization on angiogenesis of hepatocellular carcinoma cells

To evaluate the effects of four types of preoperative transcatheter arterial chemoembolization (TACE) on angiogenesis of hepatocellular carcinoma (HCC) cells. A total of 136 patients with HCC underwent liver resection. One to five courses of TACE prior to liver resection were performed in 79 patients (TACE group), in which one to four courses of chemotherapy alone were performed in 11 patients (group A); one to five courses of chemotherapy combined with iodized oil were performed in 33 patients (group B); one to three courses of chemotherapy combined with iodized oil and gelatin sponge were performed in 23 patients (group C); one to three courses of chemotherapy combined with iodized oil, ethanol and gelatin sponge were performed in 12 patients (group D). The other 57 patients only received liver resection (non-TACE group). The microvessels were marked by CD31. The expression of CD31 and vascular endothelial growth factor (VEGF) protein were detected by immunohistochemical methods. The mean microvessel density (MVD) in HCC cells was significantly higher in groups A, B, C and D than in the non-TACE group (P < 0.05). The expression of VEGF protein in HCC cells were significantly higher in groups A, B, C and D than in the non-TACE group (P < 0.05). MVD and the expression of VEGF protein were positively correlated. Mean MVD and the expression of VEGF protein were closely related to the number of courses of TACE and the interval of TACE. Four different types of preoperative TACE regimens enhanced angiogenesis in HCC cells by up-regulating the expression of VEGF protein. It is necessary to repress angiogenesis of liver cancer after TACE.