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Numerous Akt\u2010targeted therapies are being developed, the activity of Akt\u2010inhibitors is, however, strongly pH\u2010dependent. Combination therapy thus represents an opportunity to increase their efficacy. In this study, the cytotoxicity of the Akt inhibitor perifosine and the Bcl\u20102\/Bcl\u2010xL inhibitor ABT\u2010737 was tested in colon cancer HT\u201029 and HCT\u2010116 cells cultured in monolayer or in the form of spheroids. The efficacy of single drugs and their combination was analysed in different tumour\u2010specific environments including acidosis and hypoxia using a series of viability assays. Changes in protein content and distribution were determined by immunoblotting and a \u201cpeeling analysis\u201d of immunohistochemical signals. While the cytotoxicity of single agents was influenced by the tumour\u2010specific microenvironment, perifosine and ABT\u2010737 in combination synergistically induced apoptosis in cells cultured in both 2D and 3D independently on pH and oxygen level. Thus, the combined therapy of perifosine and ABT\u2010737 could be considered as a potential treatment strategy for colon cancer.<\/jats:p>","DOI":"10.1111\/jcmm.17636","type":"journal-article","created":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T06:46:46Z","timestamp":1671173206000},"page":"76-88","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Synergistic cytotoxicity of perifosine and <scp>ABT<\/scp>\u2010737 to colon cancer cells"],"prefix":"10.1111","volume":"27","author":[{"given":"Barbora","family":"Adamov\u00e1","sequence":"first","affiliation":[{"name":"Department of Experimental Biology, Faculty of Science Masaryk University  Brno Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamila","family":"\u0158\u00edhov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Experimental Biology, Faculty of Science Masaryk University  Brno Czech 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