Down-regulation of P-glycoprotein is associated with resistance to cisplatin and VP-16 in human lung cancer cell lines.

AIM

To investigate whether down-regulation of P-glycoprotein (P-gp) is correlated to resistance to cisplatin and VP-16 in four histopathological subtype cell lines of lung cancer (SK-MES-1, SPCA-1, NCI-H-460 and NCI-H-446).

MATERIALS AND METHODS

After pretreatment with or without verapamil, the P-gp expression was examined by means of RT-PCR and immunofluorescence. Cell survival on treatment with cisplatin and VP-16 was determined by MTT assay.

RESULTS

The expression of P-gp was clearly inhibited by verapamil in all four cell lines. Following pretreatment with verapamil, NCI-H-446 was more sensitive to cisplatin, while SPCA-1, NCI-H-460 and NCI-H-446 were more sensitive to VP-16 compared to the control.

CONCLUSION

Down-regulation of P-gp is associated with intrinsic resistance to cisplatin in the NCI-H-446 and to VP-16 in SPCA-1, NCI-H-460 and NCI-H-446 cell lines. These findings indicate that down-regulation of P-gp may be helpful for the reversion of drug resistance in some lung cancer cell line subtypes.