The effect of adenovirus-IkappaBalpha transduction on the chemosensitivity of lung cancer cell line with resistance to cis-diamminedichloroplatinum(II)(cisplatin) and doxorubicin(adriamycin).
Resistance to chemotherapeutic agents is the major reason for treatment failure of cancer chemotherapy. Some chemotherapeutic drugs induce the activation of NF-kappaB in cancer cells that results in their resistance to anticancer drugs. But the role of NF-kappaB in acquired resistance has not been well investigated. In this study, we transferred the "super-repressor" form of the NF-kappaB inhibitor by adenoviral vector (ad-IkappaBalpha) to human lung cancer cell lines with resistant to cisplatin (PC-14-DDP) and adriamycin (PC-14-ADR), and observed the sensitivity change. Electrophoretic mobility shift assay showed that ad-IkappaBalpha blocked the activation of NF-kappaB induced by cisplatin and adriamycin. Transduction with ad-IkappaBalpha restored the sensitivity of cisplatin and adriamycin resistant lung cancer cell lines (PC-14-DDP and PC-14-ADR) to a level compatible to the parental cell lines. Annexin-V analysis suggested that the enhancement of chemosensitivity was probably a result of the induction of apoptosis. These data demonstrated that ad-IkappaBalpha blockade of chemotherapeutic induced NF-kappaB activation increased apoptosis induction and the chemosensitivity of lung cancer cell lines with acquired resistance to cisplatin and adriamycin. Therefore, gene transfer of IkappaBalpha-SR seems to represent a new therapeutic strategy for the solution of low sensitivity and lung cancer resistance to anticancer drugs.
Lee
Choon-Taek
CT
Department of Internal Medicine and Lung Institute of Medical Research Center, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul 110-744, South Korea.
Seol
Ja Young
JY
Lee
Seok Young
SY
Park
Kyung-Ho
KH
Han
Seon Jin
SJ
Yoo
Chul-Gyu
CG
Han
Sung Koo
SK
Shim
Young-Soo
YS
Kim
Young Whan
YW
D000256:Adenoviridae; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004359:Drug Therapy, Combination; D006801:Humans; D020672:I-kappa B Proteins; D008156:Luciferases / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
D020672:I-kappa B Proteins; D004317:Doxorubicin; D008156:Luciferases; D002945:Cisplatin