en Radiation Biology Radiation Biology تحقيق بديع Original Research <div style="text-align: justify;"><span style="font-size:10pt"><span style="text-justify:newspaper"><span style="text-kashida-space:50%"><span style="line-height:119%"><span style="font-family:Calibri"><span style="color:black"><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:#1f497d"><span style="font-style:italic"><span style="font-weight:bold"><span style="language:en-US">Background</span></span></span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:#1f497d"><span style="font-weight:bold"><span style="language:en-US">:</span></span></span></span></span> <span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:black"><span style="language:en-US">The development of radiosensitizers that modulate activated signaling pathways has enhanced effective cancer treatment via radiation therapy. </span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:black"><span style="language:en-US">The phosphoinositide 3-kinases (PI3K)/protein kinase B (AKT) pathway induces cancer </span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:black"><span style="language:en-US">progression and radioresistance. Therefore, we investigated if HS-173, a novel PI3K inhibitor, could increase the radiosensitivity in breast cancer cells. </span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:#1f497d"><span style="font-style:italic"><span style="font-weight:bold"><span style="language:en-US">Materials and Methods</span></span></span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:#1f497d"><span style="font-weight:bold"><span style="language:en-US">:</span></span></span></span></span> <span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:black"><span style="language:en-US">Breast cancer cell lines (MCF-7, BT-474, and T47D, MDA-MB-231) were exposed to radiation (2</span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:#34495e"><span style="language:en-US">&ndash;</span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:black"><span style="language:en-US">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 </span></span></span></span><span lang="el" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:black"><span style="language:el">&mu;</span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:black"><span style="language:en-US">M). 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. </span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:#1f497d"><span style="font-style:italic"><span style="font-weight:bold"><span style="language:en-US">Results</span></span></span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:#1f497d"><span style="font-weight:bold"><span style="language:en-US">:</span></span></span></span></span> <span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:black"><span style="language:en-US">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 </span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:black"><span style="language:en-US">poly (ADP-ribose) polymerase (PARP-1) and cleaved </span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:black"><span style="language:en-US">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. </span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:#1f497d"><span style="font-style:italic"><span style="font-weight:bold"><span style="language:en-US">Conclusion</span></span></span></span></span></span><span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:#1f497d"><span style="font-weight:bold"><span style="language:en-US">:</span></span></span></span></span> <span lang="en-US" style="font-size:9.0pt"><span style="font-family:Calibri"><span style="color:black"><span style="language:en-US">HS-173 may be applied as a radiosensitizer with promising potential in radio-resistant breast cancer treatment.</span></span></span></span> <span lang="en-US" style="font-size:9.0pt"><span style="font-family:Tahoma"><span style="font-style:italic"><span style="language:en-US"></span></span></span></span></span></span></span></span></span></span></div> <span style="font-size:10pt"><span style="line-height:119%"><span style="font-family:Calibri"><span style="color:black">&nbsp;</span></span></span></span><br> &nbsp; PI3K, HS-173, radiosensitizer, breast cancer 347 352 http://ijrr.com/browse.php?a_code=A-10-1-915&slc_lang=en&sid=1 H. Lee 7900319475328460021581 7900319475328460021581 No Department of Medicine, College of Medicine, and Program in Biomedical Science & Engineering, Inha University, Incheon, Republic of Korea J.H. Park 7900319475328460021582 7900319475328460021582 No Department of Medicine, College of Medicine, and Program in Biomedical Science & Engineering, Inha University, Incheon, Republic of Korea K.H. Jung 7900319475328460021583 7900319475328460021583 No Department of Medicine, College of Medicine, and Program in Biomedical Science & Engineering, Inha University, Incheon, Republic of Korea J.H. Lim 7900319475328460021584 7900319475328460021584 No Department of Medicine, College of Medicine, and Program in Biomedical Science & Engineering, Inha University, Incheon, Republic of Korea S-S. Hong hongs@inha.ac.kr 7900319475328460021585 7900319475328460021585 Yes Department of Medicine, College of Medicine, and Program in Biomedical Science & Engineering, Inha University, Incheon, Republic of Korea