title: Tanshinone IIA enhances chemosensitivity of colon cancer cells by suppressing nuclear factor-κB.
abstract: The aim of the present study was to investigate the effect and molecular mechanism of tanshinone IIA (TSA) on colon cancer cells. Cell viability was determined using Cell Counting kit-8 assay and the results demonstrated that TSA treatment significantly decreased the cell viability of HCT1116 and COLO205 cells in a dose-dependent manner. TSA treatment also sensitized HCT1116 and COLO205 cells to fluorouracil therapy in a concentration-dependent manner. Western blotting was performed in order to investigate the molecular mechanisms of TSA action and determine the level of phosporylated p65 and nuclear factor-κB (NF-κB)-regulated genes, including vascular endothelial growth factor (VEGF), c-Myc, cyclooxygenase-2 (COX-2) and B-cell lymphoma-2 (Bcl-2). The results revealed that TSA treatment greatly decreased the level of phosphorylated p65 in the nucleus, which indicated the inhibition of NF-κB activation by TSA treatment. TSA also decreased the expression levels of VEGF, c-Myc, COX-2 and Bcl-2. Furthermore, the inhibition of NF-κB activation with the specific inhibitor, pyrrolidine dithiocarbamate, increased the induction of cell death and chemosensitization effect of TSA in colon cancer cells. In conclusion, these results suggest that TSA induces cell death and chemosensitizes colon cancer cells through the suppression of NF-κB signaling.
authors.affiliation: Department of Gastroenterology, Henan Provincial People's Hospital, Zhengzhou University, Zhengzhou, Henan 450003, P.R. China.
authors.forename: Yangqiu
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Department of Gastroenterology, Henan Provincial People's Hospital, Zhengzhou University, Zhengzhou, Henan 450003, P.R. China.
authors.forename: Lida
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Henan Provincial People's Hospital, Zhengzhou University, Zhengzhou, Henan 450003, P.R. China.
authors.forename: Xinhui
authors.initials: X
authors.lastname: Fang
authors.affiliation: Department of Gastroenterology, Henan Provincial People's Hospital, Zhengzhou University, Zhengzhou, Henan 450003, P.R. China.
authors.forename: Yuxiu
authors.initials: Y
authors.lastname: Yang
keywords: cell death; chemosensitization; colon cancer; nuclear factor-κB; tanshinone IIA