title: The radiation-sensitizing effect of flavopiridol in the esophageal cancer cell line Eca109.
abstract: Flavopiridol is a cyclin-dependent kinase inhibitor. It has shown an antitumor effect against several cancers. In the present study, the radiation-sensitizing effect of flavopiridol was investigated in an esophageal squamous carcinoma cell line, Eca109. The growth inhibitory rate of Eca109 with flavopiridol was determined using the MTT and the radio-sensitizing rate using clonogenic survival assays. The cell cycle distribution and the rate of apoptosis were measured using flow cytometry. The proteins cyclin D1, ERK/pERK, caspase-3, Bax and Bcl-2 were detected using western blot analysis to elucidate the mechanism of the radiosensitization effect. MTT assay showed that flavopiridol inhibited the survival rate of Eca109 cells and the effect was dose-dependent. Its IC50was 193.3 nmol/l. The result of the clonogenic survival revealed that flavopiridol enhanced the radiosensitivity of Eca109 cells and the sensitization enhancement ratio (SER) was 1.194 at 0.2×IC50.Moreover, we detected that the cells treated with flavorpiridol were arrested at the G2/M phase and the apoptosis caused by radiation was increased. In addition, the proteins caspase-3 and Bax in cells treated with flavopiridol were upregulated, while cyclin D1 and Bcl-2 were downregulated. In conclusion, flavopiridol may enhance the radiosensitivity of Eca109 cells and the radiosensitizing effect of flavopiridol may be mediated by decreasing the levels of the cyclin D1 protein, thus increasing the percentage of cells at G2/M phase.
authors.affiliation: Department of Radiology, The Second Hospital of Dalian Medical University, Dalian 116000, P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yao
authors.forename: Jingbin
authors.initials: J
authors.lastname: Shi
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Zhang
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Ruilan
authors.initials: R
authors.lastname: Ma
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
keywords: apoptosis; cell cycle; esophageal cancer; flavopiridol; radiation-sensitizing