title: Suppression of NF-κB activity by mutant IκBα: A molecular target for radiosensitization of adenoid cystic carcinoma.
abstract: The constitutive activation of the nuclear factor κB (NF-κB) signaling pathway is involved in oncogenesis, invasive growth, metastasis and induced resistance to radiation and chemotherapy. Selective inhibition of the NF-κB signaling pathway, either by a mutant inhibitor or pharmacological agents, improves the therapeutic efficiency of irradiation. In the present study, the changes in NF-κB expression and the rate of apoptosis were investigated following irradiation of cells of an adenoid cystic carcinoma cell line (ACC-M) in which NF-κB expression had been inhibited by transient transfection with a mutant IκBα plasmid. ACC-M cells were transiently transfected with the mutant IκBα plasmid using Lipofectamine and the expression of this mutant IκBα gene was verified. The presence of the mutant IκBα gene alone did not result in a reduction in cell proliferation. Furthermore, a significant inhibition of translocation and synthesis of NF-κB protein in the transfected cells was observed after irradiation. NF-κB protein was activated by different doses of irradiation in a dose- and time-dependent manner with concordant changes in the radiosensitivity of ACC-M cells. We conclude that the mutant IκBα gene selectively inhibited the NF-κB pathway, which may be a promising method to improve the radiosensitivity of adenoid cystic carcinomas.
authors.affiliation: Departments of Oral and Maxillofacial Surgery, Provincial Hospital Affiliated to Shandong University, Jinan 250021, P.R. China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Liu
authors.forename: Shengyun
authors.initials: S
authors.lastname: Huang
authors.forename: Shizhou
authors.initials: S
authors.lastname: Zhang
authors.forename: Jiawen
authors.initials: J
authors.lastname: Si
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.forename: Qiangxiu
authors.initials: Q
authors.lastname: Wang
authors.forename: Wenli
authors.initials: W
authors.lastname: Mu
authors.forename: Junqing
authors.initials: J
authors.lastname: Han
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Zhang
keywords: ACC-M cells; apoptosis; nuclear factor κB; pathway analysis; radiosensitization; transfection