PI3K/AKT inhibitor influence on the radiosensitivity of breast cancer cells / 中华放射肿瘤学杂志

ABSTRACT

Objective To evaluate whether Ly294002,suppressing phosphatidylinositol 3 kinase (PI3K)/AKT survival signaling pathway,can change the sensitivity of breast cancer cells to radiotherapy. Methods Breast cancer cultured MCF7 cells treated withradiation alone;Ly294002;or the combination of radiation and Ly294002.The inhibition of PI3K/AKT by Ly294002 was confirmed by Western blot.Clo- nogenic assay was used quantitatively to measure the mitotic cell death,and caspase-3 assay was used to e- valuate apoptosis.Results 1.Ly29400 could partially inhibit phosphorylated AKT but not radiation,the combination of both could enhance the inhibition of phosphorylated AKT,2.Timing of exposing cells to Ly294002 had some impact on clonogenic survival by radiation,one hour pre-radiation and 10 days post-ra- diation exposing to Ly294002 could maximally sensitize the cells to irradiation,3.Ly29400 combined with radiation could synergistically enhance mitotic death and apoptosis of MCF7 cells,with SER of SF_4 and D_0, being equal to 1.25 and 1.42.Conclusions PI3K/AKT pathway may be a potential target for enhancing the response of breast cancer cells to radiotherapy.