The effect of docosahexaenoic acid and 5-fluorouracil on human gastric cancer cell lines and the expression of bcl-2, bcl 2112 and bax

Objective To evaluate the growth inhibition of human gastric carcinoma cell lines SGC 7901 in vitro and the expression of bcl-2, bcl 2112 and bax with docosahexaenoic acid （DHA） and 5-fluorouracil （5-FU）. Methods The effect of DHA and 5-FU was measured by trypan blue, and the interaction between two agents was judged by combination index （ CI ）. Cells were observed by inverted microscope. Flow cytometry was used for analysis of apoptosis by PI staining and Annexin-V/PI. RT-PCR was used to analyze the levels of bcl-2, bcl 2112 and bax mRNA. Results DHA significantly inhibited the growth of SGC 7901 cells in a dose- and time-dependent way （ P 〈 0. 05 ）, the IC50 of 24 h and 48 h was 67.81μg/ml and 45.76 μg/ml, and a strong synergism was found in the combination of DHA and 5-FU （CI 〈 1 ,P 〈0. 01 ）. Treated by DHA and 5-FU for 48 h, cells became sparse under inverted microscope. DHA or 5-FU was able to induce apoptosis and the effect became even more significant by the combination of DHA and 5-FU. Cells were holted in phase of G0/G1 and S. RT-PCR showed that DHA or 5-FU downregulated the expression of bcl-2 and bcl 2112 mRNA, while bax mRNA expression was not downregulated. Conclusions DHA could inhibit the growth of gastric carcinoma cells, DHA and 5-FU had synergetic effect in the inhibition of the cells growth and blockage of the cell cycles possibly by down-regulating the expression of bcl-2 and bcl 2112. Key words: Stomach neoplasms ;  Docosahexaenoic acids ;  Fluorouracil ;  Apoptosis ;  Gene expression