Effect Of Rosiglitazone On The Expression Of Integrin β₁ In Lung Adenocarcinoma A549 Cell

Objective To investigate the molecular mechanism of Rosiglitazone on the expression of integrinβ1 in lung pulmonary carcinoma A549 cell line.Methods Human lung adenocarcinoma A549 cell line was cultured in vitro.A549 cell line was treated with various concentration of RSG or GW9662 or PD98059 or both,RT-PCR and flow cytometry methods were used to examine the expression of mRNA and cell totle protein of PPARγand integrinβ1 subunit.Results RT-PCR showed PPARγand integrinβ1 was expressed in the A549 cell line ,A549 cell was treated with 50μmol L-1 rosiglitazone after 0hours,4 hours,8hours,12hours and 24 hours,the expression of integrinβ1 reduced by rosiglitazone ,compared with the control , rosiglitazone reduce the expression of the integrinβ1 obviously in 8-hour group. The cell was treated by various concentration(0,12.5,25,50,100μmol L-1 )rosiglitazone 8 hours,compared with the control group,we found the expression of the PPARγincreased oberviously. in the 50,100μmol L-1l group.It indicated the expression of the PPARγhad the dose-dependent by rosiglitazone (P<0.05) The expression of the integrinβ1 mRNA in the 50,100μmolL-1group had dose-dependent ,the inhibition in the 100μmol L-1 group was the most(P<0.05). Compareed with the rosiglitazone(100μmol L-1)group , PPARγinhibitor GW9662 (10μmol L-1)could partly abolish the inhibition of PPARγon the expression of integrinβ1(P<0.05), ERK pathway inhibitor PD98059(20μmol L-1 )could increase the expression of integrinβ1.Flow cytometry methods were used to examine the expression of cell totle protein of integrinβ1.The cell was treated with the rosiglitazone(0,50μmolL-1,100μmolL-1),GW9662+100μmolL-1, PD98059+100μmol L-1,GW9662,PD98059 after 8 hours, the fluorescence intensity (%)of the control group was 67.8±2.22, 50,100μmol·L-1rosiglitazone group was 42.633±2.550,20.768±3.682.Compared with the 100μmol L-1 rosiglitazone group,the expression of the integrinβ1 in the PD98059+ rosiglitazone 100μmol L-1 group increased(P<0.05),but the expression of the integrinβ1 in the GW9662+ rosiglitazone 100μmol L-1 group increased.Conclusion 1)The expression of PPARγmRNA and integrinβ1 mRNA and protein had dose-dependent regulating action by Rosiglitazone(P<0.05).2)PPARγinhibitor GW9662 and ERK pathway inhibitor PD98059 could abolish the inhibition of PPARγon the expression of integrinβ1(P<0.05) .3)The effect of PPARγligand Rosiglitazone on integrinβ1 expression is mediated through PPARγ-dependent signaling parthway .4).The mechanism may be partly involved in ERK pathway .