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

  • Zhou, Li-Hong (Clinic Oncology, Putuo Hospital & Cancer Institute, Shanghai University of Traditional Chinese Medicine) ;
  • Hu, Qiang (Department of Genernal Surgery, Dahua Hospital) ;
  • Sui, Hua (Clinic Oncology, Putuo Hospital & Cancer Institute, Shanghai University of Traditional Chinese Medicine) ;
  • Ci, Shu-Jun (Clinic Oncology, Putuo Hospital & Cancer Institute, Shanghai University of Traditional Chinese Medicine) ;
  • Wang, Yan (Clinic Oncology, Putuo Hospital & Cancer Institute, Shanghai University of Traditional Chinese Medicine) ;
  • Liu, Xuan (Clinic Oncology, Putuo Hospital & Cancer Institute, Shanghai University of Traditional Chinese Medicine) ;
  • Liu, Ning-Ning (Clinic Oncology, Putuo Hospital & Cancer Institute, Shanghai University of Traditional Chinese Medicine) ;
  • Yin, Pei-Hao (Department of Genernal Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine) ;
  • Qin, Jian-Min (Department of Genernal Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine) ;
  • Li, Qi (Clinic Oncology, Putuo Hospital & Cancer Institute, Shanghai University of Traditional Chinese Medicine)
  • Published : 2012.09.30

Abstract

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

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