Objective:To observe the radiosensitivity effect of AG825 on breast cancer cell line with high expression of ERBB2 in vitro.Methods:MTT and clone formation assay were used to observe the effect of AG825 on proliferation and radiosensitivity of breast cancer line MDA-MB-453.After MDA-MB-453 was exposed to AG825 and radiation,comet assay and Western blotting were applied to detect double strand break and expressions DNA-PKcs protein,respectively.Results:AG825 inhibited proliferation rate and decrease survival fraction of MDA-MB-453.After radiation,compared with control group,expression of DNA-PKcs was lower in group with AG825 presence but double strand break was higher.Conclusion:AG825 could increase radiosensitivity of breast cancer cell line MDA-MB-453,and it may associate with its inhibition of radiation induced expression of DNA-PKcs and double strand break repair.
Bo Luo Shiying Yu Liang Zhuang Shu Xia Zhen Zhao Lei Rong
The ERBB2 nuclear transport in breast cancer cell lines after radiation and its possible role in radiation tolerance were observed. Confocal microscopy and Western blotting were applied to detect the nuclear ERBB2 expression after radiation in breast carcinomas cells. And the effects of Herceptin, AG825 and Cisplatin on the expression of nuclear ERBB2 were investigated. Survival fractions were also observed. After radiation, compared with control group, confocal microscopy and Western blot revealed that the expression of nuclear ERBB2 was increased in breast cancer cells time-dependently. Herceptin, and AG825 could significantly inhibit the radiation-induced nuclear ERBB2 expression, and decrease survival fractions. Cisplatin also induced the nuclear ERBB2 expression in breast cancer cells with high ERBB2 expression. It was concluded that radiation could induce ERBB2 nuclear transport, and nuclear ERBB2 may correlate with radiation resistance in breast cancer cells with high ERBB2 expression.
