Effect Of Metformin On Migration And Invasion Ability Of PC-3 Human Prostate Cancer Cells In Vitro And It's Mechanism

Objectives To observe the effect of different concentrations of metformin on the proliferation,migration,invasion ability of PC-3 human prostate cancer cells in vitro,and explore it's possible mechanism.Methods PC-3 prostate cancer cells were cultivated with conventional 37?,double air condition,95% humidity environment in vitro and were divided into blank control group(CK)and other groups(3.0 mg/mL metformin hydrochloride is MET1;6.0 mg/mL metformin hydrochloride is MET2;9.0 mg/mL metformin hydrochloride is MET3);To observe the proliferation activity of PC-3 cells under the action of metformin hydrochloride at different concentrations and the changes of proliferation activity of MET1,MET2,MET3 and CK cells at 24,48 and 72 h after corresponding treatment by MTT test.The migration and invasion abilities of PC-3 cells under the action of metformin hydrochloride at different concentrations were observed in vitro by the scratch test and Trans well test.The expression activity levels of Glut1,MMP-14,MMP-2,MMP-9 pathway proteins of each group of PC-3 human prostate cancer cells were observed after the corresponding treatment for 48 h by Western blotting test.SPSS Statistic 17.0 was used to analyze and process the experimental data,and evaluate the experimental results.Results 1 MTT's experimental results suggest that the proliferation capacity of cells in the MET group was lower than that in the CK group,and decreased as the concentration of metformin hydrochloride increased,and when metformin hydrochloride was applied to PC-3 cells for 24,48 and 72 h at 3.0 mg/mL,cell proliferation was significantly inhibited with the prolongation of drug action time,in other words,OD value in the MET group at 24,48 and 72 h was lower than that in the CK group,and the difference had statistically significant(P<0.05).2 The observation of cell migration in scratch experiment indicated that there was no significant difference in the proportion of scratches between the four groups immediately after the scratch test,and after 24 and 48 h of scratches,the acellular area ratio of CK group and MET1 group showed a gradual decrease,and the change value of MET1 was smaller than that of CK group,with statistical significance(P<0.05).However,there was no significant change in the proportion of acellular area in MET2 group and MET3 group at 24 and 48 h after scratch(P>0.05).At 24 and 48 h after the scratch,the MI of CK and MET1 groups showed an increasing trend,and the value of CK was greater than that of MET1,the difference was statistically significant(P<0.05).The migration index of MET2 was lower than that of MET1 group,but the change of MI was not obvious at 24 and 48 h after the scratch.MI of MET3 group was negative,and the proportion of the cell-free area increased instead of decreased after the scratch.3 Trans well test results suggested that as the concentration of metformin hydrochloride increased in cell culture medium,the number of transmembrane cells decreased gradually,in other words,the number of invasive cells was negatively correlated with the content of metformin in cell culture medium.The number of PC-3 prostate cancer cells in MET1,MET2 and MET3 groups was lower than that in CK group,with a decreasing trend,and the difference was statistically significant(P<0.05).4 Western Blotting test results suggested that the expression activities of cell proteins MMP-2,MMP-9,Glut1 and MMP-14 in the PC-3 cells of CK,MET1,MET2 and MET3 groups were successively decreased,intergroup analysis(P<0.01),there were statistically significant differences between the four group.Conclusions 1 Metformin hydrochloride can not only inhibit the proliferation,migration and invasion of PC-3 human prostate cancer cells in vitro,but also has a dosedependent and time-dependent effect.The inhibitory effect of metformin hydrochloride on the migration and invasion ability of PC-3 human prostate cancer cells in vitro may be achieved by inhibiting the Glut1/ MMP-14 / MMP-2 and MMP-9 signaling pathways.2 The ability to inhibit the proliferation,migration and invasion of PC-3 human prostate cancer cells in vitro can be improved by increasing the concentration of metformin hydrochloride in a certain range,and the inhibitory effect of MET3 group on the migration and invasion of PC-3 human prostate cancer cells in vitro is the most obvious.This may be achieved by inhibiting the expression activities of migration and invasion related proteins MMP-2,MMP-9,and Glut1,MMP-14.Figure11;Table5;Reference 100.