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Cisplatin, doxorubicin, and methotrexate are used as single agents and in triple combination. The highest level of resistance to cisplatin is observed in MG\u201063\/CISR8, doxorubicin in HOS\u2010143B\/DOXR8, and methotrexate in HOS\u2010143B\/MTXR8. The MG\u201063\/TRIR8 and HOS\u2010143B\/TRIR8 triple\u2010resistance models show lower levels of resistance to combination treatment and are not resistant to the drugs individually. Apoptosis assays suggest that the resistance in MG\u201063\/TRIR8 isfrom cisplatin and methotrexate and not doxorubicin. In contrast, the resistance in HOS\u2010143B\/TRIR8 is from doxorubicin and methotrexate instead of cisplatin. Upregulation of P\u2010glycoprotein is seen in all resistant models except those developed with single\u2010agent methotrexate. However, P\u2010glycoprotein is not causing resistance in all cell lines as the inhibitor elacridar only reverses the resistance of doxorubicin on MG\u201063\/DOXR8 and HOS\u2010143B\/TRIR8. The migration of the MG\u201063 resistant models is significantly increased, their invasion rate tends to increase, and RT\u2010PCR shows a switch from epithelial to mesenchymal gene signaling. In contrast, a significant decrease in migration is seen in HOS\u2010143B resistant models with their invasion rate tending to decrease and a switch from mesenchymal to epithelial gene signaling.<\/jats:p>","DOI":"10.1002\/adbi.202200194","type":"journal-article","created":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T12:17:33Z","timestamp":1670501853000},"source":"Crossref","is-referenced-by-count":4,"title":["Establishment and Characterization of Single and Triple\u2010Agent Resistant Osteosarcoma Cell Lines"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4275-660X","authenticated-orcid":false,"given":"Kaan","family":"Low","sequence":"first","affiliation":[{"name":"Department of Natural Sciences Middlesex University London  Hendon London NW4 4BT UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Hills","sequence":"additional","affiliation":[{"name":"Department of Natural Sciences Middlesex University London  Hendon London NW4 4BT UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen C.","family":"Roberts","sequence":"additional","affiliation":[{"name":"Department of Natural Sciences Middlesex University London  Hendon London NW4 4BT UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7892-951X","authenticated-orcid":false,"given":"Britta","family":"Stordal","sequence":"additional","affiliation":[{"name":"Department of Natural Sciences Middlesex University London  Hendon London NW4 4BT UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12,8]]},"reference":[{"key":"e_1_2_10_1_1","first-page":"69","volume":"61","author":"Jemal A.","year":"2011","journal-title":"CA \u2010 Cancer J. 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