Combination effects of tamoxifen plus 5-fluorouracil on gastric cancer cell lines in vitro.

We tested the effect of tamoxifen alone and tamoxifen plus 5-fluorouracil (5-FU) on proliferation of two different types of gastric cancer cell lines using the WST-1 method. A high dose of tamoxifen suppressed the proliferation of KATOIII cells (poorly differentiated adenocarcinoma), but MKN28 cells (well-differentiated adenocarcinoma) were not affected. The combination of the two drugs resulted in a synergistic anti-proliferative activity on KATOIII cells. On the other hand, in the combination therapy, tamoxifen stimulated MKN28 cells to proliferate in a dose-dependent manner. TGF-beta1 secretion was not changed in KATOIII cells by tamoxifen plus 5-FU treatment but was down-regulated in MKN28 cells. Both cancer cell lines were judged as intracellular estrogen receptor (ER) negative. These data suggest that the anti-proliferative effects of tamoxifen plus 5-FU on KATOIII cells were not dependent on ER expression or TGF-beta1 secretion. On the other hand, their proliferative effects on MKN28 cells might be, in part, caused by the reduced secretion of TGF-beta1.