title: CK2 inhibitors enhance the radiosensitivity of human non-small cell lung cancer cells through inhibition of stat3 activation.
abstract: CK2 interacts and phosphorylates >300 proteins, including Stat3, and is linked to a number of human cancers. Constitutively activated Stat3 has been reported in 50% of human lung cancers. Inhibition of CK2 activity can induce apoptosis and suppression of Stat3 activation in cancer cells. This study examined the effects of CK2 inhibitors on growth inhibition of lung cancer cells and the therapeutic potential on lung cancer. The CK2 inhibitor and radiation both suppressed cancer cell growth in a dose-dependent manner. Besides, the cytotoxic effect of irradiation could be augmented by CK2 inhibitors (p<0.05, two-way analysis of variance and Tukey's Honestly Significant Difference). Moreover, the growth inhibition of CK2 inhibitor and irradiation was both associated with suppression of Stat3 activation. Taken together, inhibition of CK2 activity appears to be a promising treatment strategy for non-small cell lung cancer and CK2 inhibition results in reduced Stat3 activation. Our data warrant further effort to develop CK2-targeted radiosensitizer for lung cancer treatment.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Chiayi Branch, Chiayi, Taiwan.
authors.forename: Yu-Ching
authors.initials: YC
authors.lastname: Lin
authors.forename: Ming-Szu
authors.initials: MS
authors.lastname: Hung
authors.forename: Chin-Kuo
authors.initials: CK
authors.lastname: Lin
authors.forename: Jhy-Ming
authors.initials: JM
authors.lastname: Li
authors.forename: Kuan-Der
authors.initials: KD
authors.lastname: Lee
authors.forename: Ya-Chin
authors.initials: YC
authors.lastname: Li
authors.forename: Miao-Fen
authors.initials: MF
authors.lastname: Chen
authors.forename: Jan-Kan
authors.initials: JK
authors.lastname: Chen
authors.forename: Cheng-Ta
authors.initials: CT
authors.lastname: Yang
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000532:radiotherapy*; D047390:Casein Kinase II / Q000037:antagonists & inhibitors*; D045744:Cell Line, Tumor; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy*; D011836:Radiation Tolerance; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D011838:Radiation-Sensitizing Agents; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D004815:Epidermal Growth Factor; D047390:Casein Kinase II