Methionine-dependence and combination chemotherapy on human gastric cancer cells in vitro

AIM:To elucidate whether human primary gastric cancerand gastric mucosa epithelial cells in vitro can grownormally in a rnethionine(Met)depleted environment,i.e.Met-dependence,and whether Met-depleting status canenhance the killing effect of chemotherapy on gastric cancercells.METHODS:Fresh human gastric cancer and mucosal tissueswere managed to form monocellular suspensions,whichware then cultured in the Met-free but homocysteine-containing(Met~-Hcy~+)medium,with differentchemotherapeutic drugs,The proliferation of the cells wasexamined by cell counter,flow cytometry(FCM)andmicrocytotoxicity assay(IVITT).RESULTS:The growth of human primary gastric cancer cellsin Met~-Hcy~+was suppressed,manifested by the decrease oftotal cell counts[1.46±0.42(×10~9·L-1)in Met~-Hcy~+vs.64±0.44(×10~9·L-1)in Met~+Hcy~-,P<0.01],the decline inthe percentage of G0G1phase cells(0.69±0.24 in Met~-Hcy~+vs 0.80±0.18 in Met~+Hcy~-,P<0.01)and the increase of Scells(0.24±0.20inMet~-Hcy~+vs 0.17±0.16 in Met~+Hcy~-,P<0.01);howaver,gastric mucosal cells grew normally.IfMet~-Hcy~+medium was used in combination withchemotherapeutic drugs,the number of surviving gastriccancer cells dropped significantly.CONCLUSION: Human primary gastric cancer cells in vitro are Met dependent; however, gastric mucosal cells have not shown the same characteristics. Met Hcy* environment may strengthen the killing effect of chemotherapy on human primary gastric cancer cells.