| The Effect of IkappaBalpha-SR Gene Transfer on the Sensitivity of Human Lung Cancer Cell Lines to Cisplation and Paclitaxel. |
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Seok Young Lee, Ja Young Seol, Kyung Ho Park, Gun Min Park, Yong Il Hwang, Cheol Hyeon Kim, Seung Hun Jang, Sung Youn Kwon, Chul Gyu Yoo, Young Whan Kim, Sung Koo Han, Young Soo Shim, Choon Taek Lee |
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| Abstract |
BACKGROUND
Some chemotherapeutic drugs induce NF-κB activation by degrading the IκBα protein in cancer cells which contributes to anticancer drug resistance. We hypothesized that inhibiting IκBα degradation would block NF-κB activation and result in increased tumor cell mortality in response to chemotherapy. METHODS: The "superrepressor" form of the NF-κB inhibitor was transferred by an adenoviral vector (Ad-IκBα-SR) to the human lung cancer cell lines (NCI H157 and NCI H460). With a MTT 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 IκBα-SR effectively blocked the NF-κB activation induced by cisplatin. Transduction with Ad-IκBα-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 IC50. 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-κB activation by inducing Ad-IκBα-SR, increased apoptosis and increasing the chemosensitivity of the lung cancer cell lines tested, subsequently. Gene transfer of IκBα-SR appears to be a new therapeutic strategy of chemosensitization in lung cancer. |
| Key Words:
Lung cancer, NF-κB, IκBα, adenovirus, cisplatin, paclitaxel, chemosensitization |
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