Methionine-dependence and combination chemotherapy on human gastric cancer cellsin vitro

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Abstract
AIM: To elucidate whether human primary gastric cancer and gastric mucosa epithelial cells in vitro can grow normally in a methionine (Met) depleted environment, i.e. Met-dependence, and whether Met-depleting status can enhance the killing effect of chemotherapy on gastric cancer cells. METHODS: Fresh human gastric cancer and mucosal tissues were managed to form monocellular suspensions, which were then cultured in the Met-free but homocysteine-containing (Met-Hcy+) medium, with different chemotherapeutic drugs. The proliferation of the cells was examined by cell counter, flow cytometry (FCM) and microcytotoxicity assay (MTT). RESULTS: The growth of human primary gastric cancer cells in Met-Hcy+ was suppressed, manifested by the decrease of total cell counts [1.46 ± 0.42 (× 109•L⁻¹) in Met-Hcy+vs 1.64 ± 0.44 (× 109•L⁻¹) in Met+Hcy-, P < 0.01], the decline in the percentage of G0G1 phase cells (0.69 ± 0.24 in Met-Hcy+vs 0.80 ± 0.18 in Met+Hcy-, P < 0.01) and the increase of S cells (0.24 ± 0.20 in Met-Hcy+vs 0.17 ± 0.16 in Met+Hcy-, P < 0.01); however, gastric mucosal cells grew normally. If Met-Hcy+medium was used in combination with chemotherapeutic drugs, the number of surviving gastric cancer 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.