en Other Other پژوهشي orginal article <span style="font-size:12pt"><span style="line-height:16.0pt"><span new="" roman="" style="font-family:" times=""><b><i><span style="font-size:9.0pt">Background & Aims</span></i></b><b><span style="font-size:9.0pt">: </span></b>&nbsp;<span style="font-size:9.0pt">Alpelisib and Ursolic acid are two compounds that have been shown to have potential as anti-cancer agents. Alpelisib is a selective inhibitor of the PI3K pathway, while Ursolic acid is a natural pentacyclic triterpene compound found in various plants that reveals anti-cancer, antioxidant and anti-inflammatory characteristics. The hypoxia-inducible factor 1&alpha; (HIF1&alpha;) is a transcription factor that plays a key role in regulating tumor cell survival, apoptosis, tumorigenesis and growth in low-oxygen environments. This study aims to determine the effects of Ursolic acid and Alpelisib on the expression of HIF1&alpha; gene on 4T1 cell line.</span></span></span></span><br> <span style="font-size:12pt"><span style="line-height:16.0pt"><span new="" roman="" style="font-family:" times=""><b><i><span style="font-size:9.0pt">Materials & Methods</span></i></b><b><span style="font-size:9.0pt">:</span></b><span style="font-size:9.0pt"> &nbsp;In the current experimental study, IC₅₀ concentrations of both Ursolic acid and Alpelisib were determined on 4T1 cells. Then cells were treated with determined IC₅₀ concentrations of Ursolic acid, Alpelisib and the combination of half of the IC₅₀ concentration of both drugs for 24 hours. After the treatment, viability was assessed with MTT assay and the expression of HIF1&alpha; gene was appraised by Real-time PCR. Finally, statistical analysis was accomplished by ANOVA using GraphPad Prism 8.4 software.</span></span></span></span><br> <span style="font-size:12pt"><span style="line-height:16.0pt"><span new="" roman="" style="font-family:" times=""><b><i><span style="font-size:9.0pt">Results</span></i></b><b><span style="font-size:9.0pt">:</span></b><span style="font-size:9.0pt"> &nbsp;The results of this study showed that the anti-proliferative effect of the drug combination was synergistic and concentration-dependent. The maximum decrease (74.17 % with UA and 64.04 % with Alp) in viability was observed in high doses of treatment with drugs. IC50 values of Ursolic acid and Alpelisib were 168.314 &micro;M and 6.377 &micro;M, respectively. Based on the real-time PCR results, HIF1&alpha; gene expression was significantly decreased in both single- treatment and combination groups, compared to the control group (P<0.05).</span></span></span></span><br> <span style="font-size:12pt"><span style="line-height:16.0pt"><span new="" roman="" style="font-family:" times=""><b><i><span style="font-size:9.0pt">Conclusion</span></i></b><b><span style="font-size:9.0pt">: </span></b>&nbsp;<span style="font-size:9.0pt">The results of this study showed that both Alpelisib and Ursolic acid alone or in combination with each other could have anti-cancer effects by reducing HIF1&alpha; gene expression. Further studies are needed to determine the efficacy and safety of these compounds in vivo.</span></span></span></span><br> &nbsp; 4T1 Cell Line, Alpelisib, Apoptosis, Breast Cancer, Ursolic acid 176 182 http://ijrabms.umsu.ac.ir/browse.php?a_code=A-10-296-1&slc_lang=en&sid=1 Erfan Sheikhi erfan7.sheikhi1996@gmail.com 10031947532846002138 0009-0002-9587-4407 No Department of Biochemistry, Faculty of Basic Sciences. University of Guilan, Rasht, Iran Mahmoudreza Aghamaali aghamaali@guilan.ac.ir 10031947532846002139 10031947532846002139 Yes Department of Biochemistry, Faculty of Basic Sciences. University of Guilan, Rasht, Iran Shabnam Babataheri shabnambabataheri90@gmail.com 10031947532846002140 0009-0001-4800-4751 No Faculty of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran