XL-880 increases radiosensitivity of breast cancer cells

Objective To evaluate the effects of Met inhibitor XL-880 on radiosensitivity of breast cancer cells MDA-MB-231.Methods MDA-MB-231 cell lines were assigned to the following treatment groups:control group,radiation group,XL-880 group and combination group.Cell apoptosis,cell cycle distributions and tumorigenicity were investigated by flow cytometry or clonogenic assay.The expression of apoptosis and cell cycle related proteins (p21,Cyclin B1,Bcl-2,Caspase-3 and PARP),and phosphorylation levels of c-Met were measured by Western blot.Results XL-880 combined with radiation significantly decreased the proliferation activity of MDA-MB-231 cells (P ＜ 0.05).Flow cytometry results showed that the rate of G2/M cell were increased with XL-880 (P ＜ 0.05),and the rate were (17.3 ±1.3) ％,(20.0 ± 4.0) ％,(28.5 ± 3.1) ％,(57.0 ± 3.3) ％,respectively.Annexin V/PI double-staining assay showed that XL-880 obviously induced the apoptosis of MDA-MB-231 cells after radiation (P ＜ 0.05),of which the apoptotic rates were (7.3 ±0.9)％,(14.1 ±0.6)％,(35.5 ±4.4)％,(48.2±5.3)％,respectively.XL-880 downregulated the expressions of Cyclin B1 and anti-apoptosis protein Bcl-2,while promoted the expression of apoptosis related protein cleaved Caspase-3 and PARP.Conclusions XL-880 enhance the radiosensitivity of breast cancer cell MDA-MB-231 by inhibiting Met pathway. Key words: Breast neoplasms;  Radiotherapy;  Proto-oncogene proteins c-met