Document Type : Research Articles
Authors
1
Department of Oncology, Nanjing First Hospital, Nanjing Medical University,Nanjing, Jiangsu Province, China.
2
Department of Radiation Oncology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
3
Department of Nursing, Nanjing Health College of Jiangsu Union Technical Institute, Nanjing, Jiangsu Province, China.
4
Department of Medical Imaging, Jiangsu Provincial Hospital of Traditional Chinese Medicine, Nanjing, Jiangsu Province, China.
5
Department of Medical Imaging, The Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China.
6
Department of Basic Medical Sciences, Zhejiang University, Hangzhou, Zhejiang Province, China.
7
Department of Medical Imaging, Nanjing Health College of Jiangsu Union Technical Institute, Nanjing, Jiangsu Province, China.
8
Department of Oncology, The Third Clinical Medical School of Nanjing Medical University, Nanjing First Hospital of Nanjing Medical University,Nanjing, Jiangsu Province, China.
9
Department of Oncology, The Affiliated Taikang Xianlin Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, China.
Abstract
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.
Keywords
Main Subjects
)