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Blockage of NF‐κB by IKKβ‐ or RelA‐siRNA rather than the NF‐κB super‐suppressor IκBα mutant potentiates adriamycin‐induced cytotoxicity in lung cancer cells
Author(s) -
Chen Wenshu,
Wang Xia,
Bai Lang,
Liang Xiaomin,
Zhuang Jianguo,
Lin Yong
Publication year - 2008
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21856
Subject(s) - cytotoxicity , nf κb , apoptosis , iκb kinase , cancer research , activator (genetics) , iκbα , chemistry , cancer cell , suppressor , biology , cancer , in vitro , receptor , gene , biochemistry , genetics
Ambiguous roles of genotoxic anticancer therapeutic‐induced NF‐κB activation in regulating gene expression (activation or suppression) and apoptosis (anti‐ or pro‐apoptosis) have recently been suggested. In order to clarify this controversy and determine the usefulness of NF‐κB blockage for sensitizing anticancer therapy, we have systematically investigated the effect of distinct NF‐κB‐blocking approaches on lung cancer cells' responses to Adriamycin‐induced cytotoxicity. The results show that Adriamycin‐induced NF‐κB activation functions as a transcriptional activator triggering the expression of anti‐apoptotic genes. Blocking NF‐κB with IKKβ‐ or RelA siRNA substantially sensitized Adriamycin‐induced cytotoxicity, suggesting that the NF‐κB pathway could be a target for sensitizing lung cancer cells to Adriamycin's anticancer effect. Surprisingly, although it effectively blocks NF‐κB activation, the IκBα super‐suppressor (IκBαAA) antagonized Adriamycin‐induced cell death. Additionally, the induction of death receptor 5 (DR5), which contributes to Adriamycin‐induced cytotoxicity, was not affected by NF‐κB blockage. Thus, our results suggest that Adriamycin‐induced NF‐κB is a transcriptional activator that protects lung cancer cells against apoptosis, and IKKβ‐ or RelA siRNA rather than IκBαAA is an appropriate NF‐κB blocking approach for sensitizing lung cancer cells to Adriamycin‐induced cytotoxicity. J. Cell. Biochem. 105: 554–561, 2008. © 2008 Wiley‐Liss, Inc.