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The aim of this study was designed to evaluate the anticancer activity of GSK-470, a novel\nand highly specific inhibitor of PDK1, in Pheochromocytoma (PCC) tumor model.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods:<\/jats:title>\n<jats:p>PC12 cells were xenografted into nude mice to build PCC tumor model. Animals were treated with\nGSK-470 vs vehicle. Mean tumor volume was calculated and compared across groups. TUNEL was used to\ndetect apoptosis. The effects of PDK1 inhibitor GSK-470 on activation of the Akt signaling and its downstream\nAkt\/mTOR pathway in xenotransplant tumor tissues were examined by western bolt.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results:<\/jats:title>\n<jats:p>The mean tumor volume in GSK-470 group was significantly less than that in control group. TUNEL\nresults found that cell apoptosis was markedly increased in GSK-470 group compared with the control group.\nThe western bolt analysis showed that the phosphorylation of Akt at threonine 308 was significantly reduced in\nGSK-470 group. Also, GSK-470 strongly inhibited phosphorylation of mTOR on Ser2448, a marker for\nmTORC1 activity, as well as phosphorylation of p70S6K, best characterized targets of mTOR.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion:<\/jats:title>\n<jats:p>Our results showed that GSK-470 exhibited potent anticancer activity in PC12 tumor-bearing mice.\nAlso, we found that this effect appeared to be mediated by the inhibition of the Akt\/mTOR pathway. The present\nstudy once again provides new insights into the therapeutic effects of inhibiting PDK1 in the treatment of malignant\nPCC. Therefore, we propose that GSK-470 might be an effective therapeutic agent for the treatment of\nmalignant PCC.<\/jats:p>\n<\/jats:sec>","DOI":"10.2174\/1871520620666200318100701","type":"journal-article","created":{"date-parts":[[2020,3,18]],"date-time":"2020-03-18T13:00:49Z","timestamp":1584536449000},"page":"828-833","update-policy":"https:\/\/doi.org\/10.2174\/bsp_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["PDK1 Inhibitor GSK-470 Exhibits Potent Anticancer Activity in a Pheochromocytoma PC12 Cell Tumor Model via Akt\/mTOR Pathway"],"prefix":"10.2174","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2817-709X","authenticated-orcid":true,"given":"Xiaohua","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Urology, Huashan Hospital, Fudan University, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shan","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Urology, Huashan Hospital, Fudan University, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"965","reference":[{"key":"ref=1","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1097\/CCO.0000000000000589","volume":"32","author":"Corssmit E.P.M.","year":"2020","unstructured":"Corssmit E.P.M.; Snel M.; Kapiteijn E.; Malignant pheochromocytoma and paraganglioma: management options. 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