| The aim of this experiment was to study the effect of immune adhesion moleculeβ-1 integrin on the drug-resistant tumor cells.At first, we obtained the typical A549-ADR cell strain by using different dose of ADR and increasing gradually the dose of it.The IC50 of A549-ADR is 7.45μg/ml,and the IC50 of A549 is 0.085μg/ml.The drug-resistance of A549-ADR is 87.65 times vs A549. Intersection drug sensitive experiment manifestated typical multi-drug resistance. And then, the MTT test was conducted and showed that ithe sensitive cells may inhibit drug-resistance binding with fibronectin.At the same time,we found that drug-resistance of the A549-ADR was reinforced binding with fibronectin.Blocked theβ-1 integrin with anti-β-1 integrin antibody, we found that the cell recovered the sensitivity to drug.In order to study the cause of cell,s drug-resistance,we deteced the expression of β-1 integrin for A549 and A549-ADR cell with immunohistochemical method.we found that the the expression of β-1 integrin of A549-ADR cell was much higher than that of A549(p<0.01).It was suggested that altered expression of β-1 integrin itself is the phenotype for drug-resistance.On the other hand,we deteced apoptosis with TUNEL, proved that the cells may resist apoptosis induced by chemotherapy drug if cells bind with FN, blocked theβ-1 integrin, the cell recovered the sensitivity to apoptosis.It was suggested that the destruction of the interaction of cell and ECM may invert drug-resistance.In order to study the mechanism of the cell which resist to apoptosiswhen it bind with ECM, the expression of apoptosis related gene bcl-2,bax were detected by flow cytometer. The results showed that the expression of bcl-2 rised when cell bind with ECM(62.08%),but the expression of bax was decreased(14.79%).After blocking theβ-1 integrin, the expression of bcl-2 was 23.59% and bax was 75.83%,It was opposite for two geneprotein,suggested that the interaction of cell and ECM through certain mechanism may prevent the tumor cells from a high apoptosic rate by regulating the expression of apoptosic-related genes.The sensitive cells has the same character,It was proved that the interaction of cell and ECM itself may affect the expression of bcl-2 and bax,but not the patent for drug-resistance cell. In order to study the effect of interaction on cell cycle, the interaction between cell-ECM was blocked,we found that after binding with FN,drug-resistance cells and sensitive cells arrest in G1 period with high rate,but after blocking the function of β-1 integrin, cell entered quicklly to S period. comparise with the blocking β1int experiment group,the quantity of G1 period cells of former group was high 10.24% to the latter.suggested that the cells may keeping retention in G1 period,that may postpone the process of cell cycle,perhaps it is the cause for the cell drug-resistance.Through the study,we draw a conclusion that β1int binding with ECM is one of the cause for drug-resistance of tumor cells; The interaction of β1int and ECM abtain drug-resistance mainly through inhibiting apoptosis and impacting cell cycle; The interaction of β1int and ECM may upregulate the expression of apoptosis-related gene Bcl-2 and downgulate the Bax.It became the drug -resistance phenotype for the increasing of the expression of β1int;Blocking the interaction of β1int and ECM may reverse drug-resistance.
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