The Effect of IkappaBalpha-SR Gene Transfer on the Sensitivity of Human Lung Cancer Cell Lines to Cisplation and Paclitaxel

Background : Some chemotherapeutic drugs induce NF- activation by degrading the protein in cancer cells which contributes to anticancer drug resistance. We hypothesized that inhibiting degradation would block NF- activation and result in increased tumor cell mortality in response to chemotherapy. Methods : The "superrepressor" form of the NF- inhibitor was transferred by an adenoviral vector (Ad--SR) to the human lung cancer cell lines (NCI H157 and NCI H460). With a MIT assay, the level of sensitization to cisplatin and paclitaxel were measured. To confirm the mechanism, an EMSA and Annexin V assay were performed. Results : EMSA showed that -SR effectively blocked the NF- activation induced by cisplatin. Transduction with Ad--SR resulted in an increased sensitivity of the lung cancer cell lines to cisplatin and paclitaxel by a factor of 2~3 in terms of . Annexin-V analysis suggests that this increment in chemosensitivity to cisplatin probably occurs through the induction of apoptosis. Conclusion : The blockade of chemotherapeutics induced NF- activation by inducing Ad--SR, increased apoptosis and increasing the chemosensitivity of the lung cancer cell lines tested, subsequently. Gene transfer of -SR appears to be a new therapeutic strategy of chemosensitization in lung cancer.