Effect Of Bisphenol A On Growth And Invasion Of Gastric Cancer Cells

Objective: To clarify the effect of environmental endocrine disruptor bisphenol A(BPA) on gastric cancer cell growth, invasiveness and analyze the potential mechanisms.Methods: We selected the moderately and poorly differentiated gastric cancer cell line(SGC-7901, MKN-45) to adherently culture in vitro. After treated by BPA at the dose of 10-10~10-4mol/L, the cell growth and morphology were observed at 24, 48 and 72 h. The CCK-8 assay was employed to detect cell proliferation or inhibition. Using Transwell invasion assay to observe the effect of BPA on gastric cancer cell invasion ability and using RT-PCR(reverse transcriptase polymerase chain reaction) to detect the m RNA expression of invasion-related gene MMP-9 in gastric cancer cells. To confirm weather the estrogen receptor pathway play a role in gastric cancer invasiveness enhanced by BPA, we used the estrogen receptor antagonist fulvestrant(ICI 182,780)as a control.Results: 10-10~10-5 mol/L BPA were observed to limit the two kinds of gastric cancer cell growth; As the concentration gradient increased, the cells were more discrete and the cell connection became weak and the contact became less; In addition, 10-4 mol/L BPA has toxic effect on cells. The result of Transwell invasion assay of gastric cancer cell line SGC-7901: the invasive ability of BPA group cells were enhanced compared with control(134.60% ? 14.91% vs100.00% ?16.16%, p<0.01, n=3), but BPA+ICI group comparing to BPA group cells, ICI group cells comparing to control showed no significant difference(p>0.05, n=3); gastric cancer cell line MKN-45: the invasive ability of BPA group cells were enhanced compared with control(120.06% ?15.19% vs 100.00% ?16.26%, p<0.05, n=3), but BPA+ICI group comparing to BPA group cells, ICI group cells comparing to control showed no significant difference(p>0.05, n=3).On gene research level of gastric cancer cell line SGC-7901: compared with control, the mRNA expression level of MMP-9 in 10-5 mol/L and 10-6 mol/L BPA group cells were significantly increased(p<0.05, n=3), but that of BPA+ICI group comparing to BPA group cells showed no significant difference(p>0.05, n=3); Gastric cancer cell line MKN-45: compared with control, themRNA expression level of MMP-9 in 10-5 mol/L, 10-6 mol/L and 10-7 mol/L BPA group cells showed significantly increased(p<0.01, n=3), but that of BPA+ICI group comparing to BPA group cells were the same as SGC-7901(p>0.05, n=3).Conclusions: Within a certain range of concentrations, BPA can cause gastric cancer cell growth abnormalities. With the BPA concentration increased, the invasion ability of gastric cancer cells was enhanced. MMP-9, which is a invasion-related gene, was involved in the invasion of gastric cancer cells enhanced by BPA. ER pathway may negatively regulate this process.