Purpose: To study the effect of transforming growth factor (TGF)-β1 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-β1 had a significant effect on blocking the cancer cell growth (p<0.05). TGF-β1 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-β1-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-β1 (p<0.05). N-acetylcysteine (NAC) treatment almost completely eliminated the reactive oxygen species (ROS) produced by TGF-β1 and ERK activation. Compared with administration of 5-FU or etoposide alone, TGF-Β1 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-β1.