Document Type: Research Articles
Department of Oncology, Nanjing First Hospital, Nanjing Medical University,Nanjing, Jiangsu Province, China.
Department of Radiation Oncology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
Department of Nursing, Nanjing Health College of Jiangsu Union Technical Institute, Nanjing, Jiangsu Province, China.
Department of Medical Imaging, Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing, Jiangsu Province, China.
Department of Medical Imaging, The Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China.
Department of Basic Medical Sciences, Zhejiang University, Hangzhou, Zhejiang Province, China.
Department of Medical Imaging, Nanjing Health College of Jiangsu Union Technical Institute, Nanjing, Jiangsu Province, China.
Department of Oncology, The Third Clinical Medical School of Nanjing Medical University, Nanjing First Hospital of Nanjing Medical University,Nanjing, Jiangsu Province, China.
Department of Oncology, The Affiliated Taikang Xianlin Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, China.
Objective: This study was undertaken to investigate the effect of C225 on the radio-sensitivity of MDA-MB-231 cells
line and to disclosure underlying mechanism. Methods: CCK8 assay was used to measure the proliferation inhibition
of C225 on MDA-MB-231 cells. The combined effects of C225 plus radiation on the proliferation of MDA-MB-231
cells were also evaluated by CCK-8 assay. The clonogenic assay was performed to evaluate the cell surviving fractions
and to determine the radio-sensitizing effect of C225 on MDA-MB-231 cells. The apoptosis and cell cycle distribution
were analyzed by flow cytometry. Western blot analysis was used to detect the expression of p-EGFR, p-Akt, p-P38, and
caspase-3. Results: C225 had an inhibiting effect on the proliferation of cells in a concentration-dependent manner. The
cloning formation capacity was decreased in C225 plus radiation group. C225 increased radio-sensitivity of cells and
led to cell cycle arrest in G0/G1 phase markedly. Cells treated with C225 and radiation predominantly exhibited G0/G1
phase arrest and significant decreased in the fraction of cells in the S phase. Moreover, C225 and radiation significantly
increased the apoptosis rate of cells. Decreased cell proliferation was further supported by the down-regulation of p-EGFR
and its downstream singling pathway proteins such as p-Akt and p-P38. The up-regulation of the Caspase-3 expression
in C225 plus radiation group revealed that C225 could increase radiation-inducing cell apoptosis. Conclusion: C225
could increase the radio-sensitivity of cells, which may be due to the anti-proliferative synergistic effect between C225
and radiation as well as the down-regulation of the PI3K/Akt signaling pathway.