Association of lovastatin overcoming gefitinib resistance with integrin β1 and survivin / 第二军医大学学报

ABSTRACT

Objective To investigate the association of lovastatin overcoming gefitinib resistance with the levels of integrin β1 and Survivin in human non-small cell lung cancer (NSCLC) cell line PC9 in vitro, and to explore the possible mechanism. Methods The NSCLC cell line PC9 with acq uired gefitini-resistance were divided into 4 groups; control group (RPM1 1640), gefitinib group (1 /μmol/L gefitinib), lovastatin group (5 μmol/L lovastatin), and gefitinib combined with lovastatin group (1 μmol/L gefitinib+5 /μmol L lovastatin). After treatment with different drugs in each group, the inhibition of cell proliferation was detected by cell counting kit-8 (CCK-8) test, the levels of integrin ft 1 and Survivin mRNA were detected by PCR, and the expressions of integrin (31 and Survivin protein were detected by Western blotting analysis. Results Compared with the control group, lovastatin group and gefitinib group, lovastatin combined with gefitinib treatment had significantly inhibited proliferation of PC9 cells with acquired gefitinib-resistance (P<0. 01), and the expressions of integrin)31. Survivin protein and mRNA in PC9 cells were significantly decreased in the three groups (P<0. 05, P<0. 01). Conclusion Mechanisms of lovastatin combined with gefitinib in overcoming gefitinib resistance may be through blocking integrin β1-p-Akt-Survivin signaling pathway, indicating that the combination treatment might be an effective strategy for gefitinib resistance.