The Combined Effect And Antitumor Mechanism Of Sodium Arsenite And 10-Hydroxycamptothecine (HCPT) On Human Gastric Carcinoma Cell Lines In Vitro

Objective: To study the combined effect and antitumor mechanism of sodium arsenite and HCPT on human gastric carcinoma cell lines BGC-823 and SGC-7901 in vitro.Methods: MTT assay was used to analyze the effect of sodium arsenite and HCPT Alone or in combination on the growth of BGC-823 and SGC-7901 cells. Light microscopy, electron microscopy, flow cytometry, and immunocytochemical staining were used to observe the changes in morphologic , cell cycle and the expression of Caspase-3 nm23 . E-cadherin of these cells.Results:1. Alone or in combination sodium arsenite and HCPT could inhibit the growth of BGC-823 and SGC-7901 cells in a time and dose dependent fashion. The combination of sodium arsenite and HCPT had synergistic effect on BGC-823 cells as inhibition rate ranged from 45% to 90%. The combination of sodium arsenite and HCPT had synergistic effect on SGC-7901 cells as inhibition rate ranged from 60% to 90%.2. BGC-823 and SGC-7901 cells presented some morphologic features ofapoptosis and necrosis after 72 hours exposure to sodium arsenite or HCPT .3. Sodium arsenite could arrest cell cycle of BGC-823 and SGC-7901 cells in S phase and HCPT could arrest cell cycle of these cells in S and G2/M phase respectively.4. Both sodium arsenite and HCPT could upgrade the expression of Caspase-3 of BGC-823 and SGC-7901 cells and induce the expression of nm23 of these cells. Both of them had no obvious effect on the expression of E-cadherin of these cells.Conclusion:1. Alone or in combination sodium arsenite and HCPT could inhibit the growth of human gastric carcinoma cells effectively . The combination of them showed synergistic effect at relatively high concentration.2. Although they had a different antitumor mechanism, the two drugs had similar effect on induction of cell death , arrest of cell cycle, upgrade of the expression of apoptosis-related protein and induction of the expression of differentiation-metastasis related protein.The combination of the two drugs is practical according to the compose principle of the combination chemotherapy regimens. There are good prospect of combined use of sodium arsenite and HCPT for tumor therapy.