Effect of TGF-β1 on apoptosis of colon cancer cells via the ERK signaling pathway

Purpose: To study the effect of transforming growth factor (TGF)-beta 1 on apoptosis of colon cancer cells via the ERK signaling pathway. Methods: Human chemosensitive colon cancer cell line HT-29 was used in this study. VEGF mRNA and protein level were detected using PCR and western blot. Enzyme-linked immunosorbent assay (ELISA) was used for prostaglandin (PG) detection. Cell proliferation was determined via MTT assay. Results: TGF-beta 1 had a significant effect on blocking the cancer cell growth (p<0.05). TGF-beta 1 significantly reduced the VEGF mRNA level (p<0.05) and eliminated the COX-2 expression in a dose-dependent manner, while p53 expression was increased (p<0.05). TGF-beta 1-induced inhibitory effect on COX-2 was significantly eliminated by the ERK inhibitor Compound C (p<0.05). The basal PGE2 production was eliminated in cells treated with TGF-beta 1 (p<0.05). N-acetylcysteine (NAC) treatment almost completely eliminated the reactive oxygen species (ROS) produced by TGF-beta 1 and ERK activation. Compared with administration of 5-FU or etoposide alone, TGF-beta 1 combined with 5-FU or etoposide significantly administration the viability of colon cancer HT-29 cells. Conclusion: ERK is a newly-identified cancer target molecule, which can significantly control COX-2 in colon cancer cells treated with TGF-beta 1.