EGFR inhibitor C225 Increases the Radio-Sensitivity of Human Breast Cancer Cells

Abstract

Objective: This study was undertaken to investigate the effect of C225 on the radio-sensitivity of MDA-MB-231 cells<br />line and to disclosure underlying mechanism. Methods: CCK8 assay was used to measure the proliferation inhibition<br />of C225 on MDA-MB-231 cells. The combined effects of C225 plus radiation on the proliferation of MDA-MB-231<br />cells were also evaluated by CCK-8 assay. The clonogenic assay was performed to evaluate the cell surviving fractions<br />and to determine the radio-sensitizing effect of C225 on MDA-MB-231 cells. The apoptosis and cell cycle distribution<br />were analyzed by flow cytometry. Western blot analysis was used to detect the expression of p-EGFR, p-Akt, p-P38, and<br />caspase-3. Results: C225 had an inhibiting effect on the proliferation of cells in a concentration-dependent manner. The<br />cloning formation capacity was decreased in C225 plus radiation group. C225 increased radio-sensitivity of cells and<br />led to cell cycle arrest in G0/G1 phase markedly. Cells treated with C225 and radiation predominantly exhibited G0/G1<br />phase arrest and significant decreased in the fraction of cells in the S phase. Moreover, C225 and radiation significantly<br />increased the apoptosis rate of cells. Decreased cell proliferation was further supported by the down-regulation of p-EGFR<br />and its downstream singling pathway proteins such as p-Akt and p-P38. The up-regulation of the Caspase-3 expression<br />in C225 plus radiation group revealed that C225 could increase radiation-inducing cell apoptosis. Conclusion: C225<br />could increase the radio-sensitivity of cells, which may be due to the anti-proliferative synergistic effect between C225<br />and radiation as well as the down-regulation of the PI3K/Akt signaling pathway.