Objective: To investigate the relationship between p53 mutation and the expression of some drug-resistance genes commonly found in lung cancer.
Methods: Sixty-six of untreated lung cancers and paracancerous tissues were obtained by surgical resection. Immunohistochemical staining was employed for detection of both mutant p53 and drug-resistance associated proteins (MDR1, MRP1, LRP, TOPO II alpha, GST-pi), PCR-SSCP and RT-PCR were used for detection of mutations of p53 exon 5-8 as well as the expression of mRNAs for the genes coding those drug-resistance associated proteins in 31/66 cases. ATP-TCA assay was also performed simultaneously in 12 out of the 31 cases for evaluation of their reaction in response to chemotherapy.
Results: Correlations were found between p53 mutation and expression of either Pgp or MRP1 or GST-pi (P < 0.05). There was a significant correlation between p53 mutation with simultaneous expression of Pgp and MRP1 and drug-resistance to either vinorelbine or carboplatin.
Conclusions: The results suggested that p53 mutation in lung cancers was closely correlated with the expression of drug-resistance associated protein which was associated with endogenous resistance to most of chemotherapeutic drugs. It indicated that wild p53 gene therapy might be helpful for treating the endogenous drug resistance of lung cancer in chemotherapeutics.