OBJECTIVETo investigate the effects of n-3 polyunsaturated fatty acids(n-3PUFA) on human colorectal cancer cell line HT-29 and associated mechanism.

METHODSThe effects of docosahexaenoic acid (DHA) on the proliferation and apoptosis on HT-29 human colorectal cancer cells were evaluated by MTT assay, cell morphology (Hoechst33258 dyeing), DNA gel electrophoresis, and flow cytometry. The content of n-6PUFA and n-3PUFA of the treated cells and the ratio of n-6/n-3PUFA were analyzed by chromatography.

RESULTSDHA effectively inhibited HT-29 cell proliferation in a dose- and time-dependent manner. The proliferative inhibition rates of HT-29 cells treated with 10, 20, 40, and 80 mg/L DHA for 24 hours were 16.8%, 24.7%, 50.0%, and 60.1%, respectively, while the inhibition rates were 50.0%, 69.9%, and 77.0% respectively when HT-29 cells were treated with 40 mg/L DHA for 24, 48, and 72 hours. The typical apoptotic morphologic changes of HT-29 cells could be observed, including chromatin margination, nuclear condensation and apoptotic bodies. Gel electrophoresis of DNA degradation displayed typical DNA ladder fragments. HT-29 cells treated with DHA were arrested in G1 phase and the proportion of HT-29 cells in Gl phase increased compared with that of the control group (72.1% vs. 51.3%) while the proportion of the cells in S phase decreased significantly (19.9% vs. 38.9%). The content of n-6PUFA decreased, n-3PUFA content increased and the ratio of n-6/n-3PUFA lowered significantly in colorectal cancer cells treated with DHA (P<0.01).

CONCLUSIONSn-3PUFA can inhibit the growth of human colorectal cancer cells via inhibition of the proliferation and induction of apoptosis. These effects may be associated with decrease in n-6/n-3PUFA ratio.