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HS-173, a novel PI3K inhibitor enhances radiosensitivity of breast cancer cells
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| H. Lee, J.H. Park, K.H. Jung, J.H. Lim, S-S. Hong |
| Department of Medicine, College of Medicine, and Program in Biomedical Science & Engineering, Inha University, Incheon, Republic of Korea , hongs@inha.ac.kr |
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Abstract: (778 Views) |
Background: The development of radiosensitizers that modulate activated signaling pathways has enhanced effective cancer treatment via radiation therapy. The phosphoinositide 3-kinases (PI3K)/protein kinase B (AKT) pathway induces cancer progression and radioresistance. Therefore, we investigated if HS-173, a novel PI3K inhibitor, could increase the radiosensitivity in breast cancer cells. Materials and Methods: Breast cancer cell lines (MCF-7, BT-474, and T47D, MDA-MB-231) were exposed to radiation (2–8 Gy). After irradiation, cell viability was assessed using the MTT assay. MDA-MB-231 cells were exposed to radiation (5 Gy) alone and/or in combination with HS-173 (1 μM). After treatment, the levels of PI3K/AKT signaling protein were measured using western blotting. The radiosensitivity of HS-173 was assessed using a clonogenic assay and flow cytometry. Results: We observed that HS-173 decreased the radiation-induced phosphorylation of AKT in MDA-MB-231 cells and increased their radiosensitivity in the clonogenic assay. Upon investigation of the mechanism underlying the enhanced radiosensitivity by HS-173, we observed a significant increase in the IR-induced G2/M cell cycle arrest and apoptosis pathway components, including poly (ADP-ribose) polymerase (PARP-1) and cleaved caspase-3. It can be concluded that HS-173 significantly improved radiosensitivity by inducing apoptosis and G2/M arrest in radio-resistant breast cancer cells. Conclusion: HS-173 may be applied as a radiosensitizer with promising potential in radio-resistant breast cancer treatment.
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| Keywords: PI3K, HS-173, radiosensitizer, breast cancer |
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Full-Text [PDF 1768 kb]
(336 Downloads)
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Type of Study: Original Research |
Subject:
Radiation Biology
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