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However, considerable side effects and the emergence of drug resistance are becoming critical limitations to its application. Combinatorial strategies may be able to extend the use of cisplatin. Both Tanshinone IIA and cisplatin inhibit non\u2010small\u2010cell lung cancer cell growth in a time\u2010 and dose\u2010dependent manner. When Tanshinone IIA was combined with cisplatin at a ratio of 20:1, they were observed to exert a synergistic inhibitory effect on non\u2010small\u2010cell lung cancer cells. The combination treatment was shown to impair cell migration and invasion, arrest the cell cycle in the S phases, and induce apoptosis in A549 and PC9 cells in a synergistic manner. KEGG pathway analysis and molecular docking indicated that Tanshinone IIA might mainly influence the phosphatidylinositol 3\u2010kinase\u2010Akt signalling pathway. In all treated groups, the expression levels of Bax and cleaved Caspase\u20103 were up\u2010regulated, whereas the expression levels of Bcl\u20102, Caspase\u20103, p\u2010Akt, and p\u2010PI3K proteins were down\u2010regulated. Among these, the combination of Tan IIA and cisplatin exhibited the most significant difference. Tanshinone IIA may function as a novel option for combination therapy for non\u2010small\u2010cell lung cancer treatment.<\/jats:p>","DOI":"10.1002\/ptr.6392","type":"journal-article","created":{"date-parts":[[2019,7,3]],"date-time":"2019-07-03T06:36:26Z","timestamp":1562135786000},"page":"2298-2309","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Tanshinone IIA combined with cisplatin synergistically inhibits non\u2010small\u2010cell lung cancer in vitro and in vivo via down\u2010regulating the phosphatidylinositol 3\u2010kinase\/Akt signalling pathway"],"prefix":"10.1002","volume":"33","author":[{"given":"Xiao\u2010Zhong","family":"Liao","sequence":"first","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital of Guangzhou University of Chinese Medicine  Guangzhou China"},{"name":"Department of Oncology The First Affiliated Hospital, Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital, Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery The First Affiliated Hospital of Nanchang University  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuang\u2010Zhong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital of Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling\u2010Ling","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital of Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia\u2010Hui","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital, Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han\u2010Rui","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital of Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital of Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia\u2010Xing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital, Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8283-6554","authenticated-orcid":false,"given":"Li\u2010Zhu","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Oncology The First Affiliated Hospital of Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,7,3]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12918-018-0606-6"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.19201"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1875-5364(15)30075-3"},{"issue":"267976","key":"e_1_2_12_5_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2014\/267976","article-title":"Anti\u2010inflammatory and immunomodulatory mechanism of Tanshinone IIA for atherosclerosis","volume":"2014","author":"Chen Z.","year":"2014","journal-title":"Evidence\u2010based Complementary and Alternative Medicine: Ecam"},{"issue":"2","key":"e_1_2_12_6_1","first-page":"231","article-title":"Tanshinone IIA induces apoptosis in human lung cancer A549 cells through the induction of reactive oxygen species and decreasing the mitochondrial membrane potential","volume":"25","author":"Chiu T. 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