Tanshinone II-A Inhibits Angiogenesis through Down Regulation of COX-2 in Human Colorectal Cancer

Abstract

Angiogenesis plays a significant role in colorectal cancer (CRC) and cyclooxygenase-2 (COX-2) appears tobe involved with multiple aspects of CRC angiogenesis. Our aim was to investigate the inhibitory effects of TanII-A (Tanshinone II-A, Tan II-A) on tumor growth in mice, as well as alteration of expression of COX-2 andVEGF in CRC. We established the mice xenograft model of C26 CRC cell line, and injected 0.5, 1, 2mg/kg ofTan II-A and 1mg/kg of 5-FU in respectively in vivo. Then, we assayed tumor weight and volume, and evaluatedmicrovascular density and expression of VEGF. COX-2 promoter and COX-2 plasmids were transfected intoHCT-116 cells, followed by detection of COX-2 promoter activity by chemiluminescence, and detection of COX-2mRNA expression by fluorescence quantitative PCR. Taken together, the results showed Tan II-A could inhibittumor growth and suppress the VEGF level in vivo. HCT-116 cell experiments showed marked inhibitory effectsof Tan II-A on COX-2 and VEGF in a dose-dependent manner. The results indicate that Tan II-A can effectivelyinhibit tumor growth and angiogenesis of human colorectal cancer via inhibiting the expression level of COX-2and VEGF.