Open AccessThe novel mTORC1/2 dual inhibitor INK128 enhances radiosensitivity of breast cancer cell line MCF-7
Author(s) -
Zhi Gang Liu,
Jiao Tang,
Zhenghu Chen,
Huiyuan Zhang,
Hui Wang,
Jianhua Yang,
Hong Zhang
Publication year - 2016
Publication title -
international journal of oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.405
H-Index - 122
ISSN - 1019-6439
DOI - 10.3892/ijo.2016.3604
Subject(s) - radiosensitivity , cell cycle , cancer research , biology , mcf 7 , pi3k/akt/mtor pathway , viability assay , clonogenic assay , radioresistance , cell growth , cancer , cell , cancer cell , cell culture , radiation therapy , medicine , microbiology and biotechnology , signal transduction , biochemistry , genetics , human breast
mTOR, a member of the PIKK family, is crucial for cell growth, survival, motility, proliferation, protein synthesis and DNA transcription. Many studies have demonstrated that mTOR inhibitor could enhance radiosensitivity. However, the effect of the novel mTORC1/2 dual inhibitor, INK128, on the radiosensitivity of breast cancer and the underlying mechanisms are still vague. In the present study, the cell viability was estimated using CCK-8 assay, and the dose-survival relationship was analyzed using a clonogenic survival assay. Cell cycle was evaluated by flow cytometry. The staining of γH2AX foci was assessed by immunofluorescence. In addition, we used western blots to verify the downregulating signal protein and to detect the potential related pathway. We found that the exposure of MCF-7 cells to INK128 decreased the cell viability. Exposure of MCF-7 cells to INK128 and combined ionizing radiation greatly reduced the survival rate. INK128 combined radiotherapy significantly induced G2/M arrest, double strand breaks and inhibited its repair. Furthermore, INK128 plus radiation downregulated p-Chk2, p21 and upregulated cleaved PARP, LC3B expression. These findings suggest that mTOR inhibitor could be used as a novel radiosensitizing target for breast cancer patients.