The Effect of IkappaBalpha-SR Gene Transfer on the Sensitivity of Human Lung Cancer Cell Lines to Cisplation and Paclitaxel.
10.4046/trd.2001.51.2.122
- Author:
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
- Publication Type:Original Article
- Keywords:
Lung cancer;
NF-κB;
IκBα;
adenovirus;
cisplatin;
paclitaxel;
chemosensitization
- MeSH:
Adenoviridae;
Annexin A5;
Apoptosis;
Cell Line*;
Cisplatin;
Drug Resistance;
Drug Therapy;
Humans*;
Inhibitory Concentration 50;
Lung Neoplasms*;
Lung*;
Mortality;
Paclitaxel*
- From:Tuberculosis and Respiratory Diseases
2001;51(2):122-134
- CountryRepublic of Korea
- Language:Korean
-
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.
