HS-173, a novel PI3K inhibitor enhances radiosensitivity of breast cancer cells

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.