The method of xenograft tumor volume measurement, radiation and reagent administration are described in Methods section. The tumor volumes in the ABT-737 plus radiation Poziotinib research buy group were significant smaller than those in the DMSO plus radiation group (P < 0.01). However, the growth curves of the tumors in the DMSO group, the DMSO plus radiation group and the ABT-737 group were very similar. In this study, six mice per group were used. Points, mean volumes; bars, SD. Discussion Fractionated radiation (FR) is used often in radiotherapy treatment to facilitate the recovery of normal tissues,

while the repair of cancer cells is generally less efficient between fractions. However, the acquired radioresistance of cancer

cells is thought to occur during the repopulation of the tumor during the long-term FR [19]. The proliferating cancer cells that repopulate the tumor may be different subpopulation with a different genotype that confers radioresistance. Cancer cells with acquired radioresistance many survive during radiotherapy and lead to additional cancer recurrence Ceritinib nmr after radiation therapy, thus limiting the effectiveness of radiation therapy. Therefore, to promote better outcomes for patients undergoing radiotherapy, an effective strategy may be to target the cells acquired radioresistance. In the present study, the MDA-MB-231R cells were obtained after fractionated radiation with total dose of 50 Gy and were cultured without radiation for the next 10 passages. The radioresistance

of MDA-MB-231R cell line was determined using a colony-forming assay. The results of Western blot analysis showed that the anti-apoptotic proteins Bcl-2 and Bcl-xL Fossariinae were overexpressed in the MDA-MB-231R cells that had acquired radioresistance. RT-PCR analysis confirmed that the expression of the anti-apototic genes Bcl-2 and Bcl-xL were upregulated in the radioresistant MDA-MB-231R cells and overexpressed compared with their parental cell line. The overexpression of anti-apoptotic proteins in the Bcl-2 family is frequently observed in many different tumor types and has been associated with resistance to radiotherapy [20, 21]. However, the molecular mechanism underlying the acquired radioresistance of cancer cells remains unclear. Several mechanisms are thought to contribute to the acquired radioresistance, including mutated p53 [22], amplification of DNA repair genes [23], overexpression of the cell-cycle regulator protein, cyclin D1 [19] and activation of pro-survival oncogenes such as EGFR [24]. The overexpression of Bcl-2 and Bcl-xL in the MDA-MB-231R cells indicated that these anti-apoptotic proteins play an important role in the acquisition of radioresistance. The expression of anti-apoptotic proteins is closely related to the radiosensitivity of cancer cells, and targeting these proteins could be an effective method to overcome radioresistance. An et al.