{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T02:44:24Z","timestamp":1785725064696,"version":"3.56.0"},"reference-count":116,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004442","name":"National Science Centre","doi-asserted-by":"publisher","award":["2020\/37\/B\/NZ6\/03435"],"award-info":[{"award-number":["2020\/37\/B\/NZ6\/03435"]}],"id":[{"id":"10.13039\/501100004442","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2020\/37\/B\/NZ6\/03435"],"award-info":[{"award-number":["2020\/37\/B\/NZ6\/03435"]}],"id":[{"id":"https:\/\/ror.org\/03ha2q922","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Despite the development of new drugs, chemoresistance constitutes a major obstacle in cancer treatment. To investigate mechanisms of resistance and potential therapeutic targets, we developed doxorubicin-resistant models of HER2\u2212 (D2F2\/Dox) and HER2+ (D2F2E2\/Dox) breast cancer cells. Compared with parental cells, the D2F2\/Dox and D2F2E2\/Dox differed in morphology, increased migratory potential, elevated levels of the transcription factor signal transducer and activator of transcription 3 (Stat3), and a lower proliferation rate in D2F2E2\/Dox. Moreover, D2F2\/Dox and D2F2E2\/Dox differed in the expression profiles of genes related to cell stemness, apoptosis, and drug efflux. Stat3 gene silencing in both doxorubicin-resistant cell types reversed the expression profiles of some genes (different in each resistant cell line), and decreased migratory potential was observed only in D2F2 cells. These data indicate that the acquired doxorubicin resistance was associated with Stat3 status; however, HER2\u2212 and HER2+ breast cancer cells did not indicate the same mechanism of chemoresistance acquisition. Importantly, Stat3 silencing did not substantially restore doxorubicin sensitivity, suggesting that effective therapy may require simultaneous targeting of multiple pathways. Furthermore, we demonstrated that siStat3 therapeutics could be selectively delivered to HER2+ cancer cells using H2.1MS1:MS2KN silk spheres, indicating their potential for targeted drug delivery in vivo.<\/jats:p>","DOI":"10.3390\/cells15151393","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T01:43:27Z","timestamp":1785721407000},"page":"1393","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Development of a Doxorubicin Resistance Model in HER2\u2212 and HER2+ Breast Cancer to Analyze Potential Therapy Targets and Drug Delivery Methods"],"prefix":"10.3390","volume":"15","author":[{"given":"Sara","family":"Molenda","sequence":"first","affiliation":[{"name":"Department of Cancer Immunology, Poznan University of Medical Sciences, 60-806 Poznan, Poland"},{"name":"Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Centre, 61-866 Poznan, Poland"},{"name":"Doctoral School, Poznan University of Medical Sciences, 61-701 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Gryska","sequence":"additional","affiliation":[{"name":"Department of Cancer Immunology, Poznan University of Medical Sciences, 60-806 Poznan, Poland"},{"name":"Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Centre, 61-866 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4985-9321","authenticated-orcid":false,"given":"Igor","family":"Piotrowski","sequence":"additional","affiliation":[{"name":"Department of Medical Physics, Greater Poland Cancer Centre, 61-866 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agata","family":"Kubicka","sequence":"additional","affiliation":[{"name":"Department of Tumour Pathology and Prophylaxis, Poznan University of Medical Sciences, 61-866 Poznan, Poland"},{"name":"Department of Cancer Pathology, Greater Poland Cancer Centre, 61-866 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agata","family":"Sikorska","sequence":"additional","affiliation":[{"name":"Department of Cancer Immunology, Poznan University of Medical Sciences, 60-806 Poznan, Poland"},{"name":"Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Centre, 61-866 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0497-3726","authenticated-orcid":false,"given":"Tomasz","family":"Deptuch","sequence":"additional","affiliation":[{"name":"Department of Cancer Immunology, Poznan University of Medical Sciences, 60-806 Poznan, Poland"},{"name":"Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Centre, 61-866 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2349-419X","authenticated-orcid":false,"given":"Hanna","family":"Dams-Kozlowska","sequence":"additional","affiliation":[{"name":"Department of Cancer Immunology, Poznan University of Medical Sciences, 60-806 Poznan, Poland"},{"name":"Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Centre, 61-866 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/s41572-019-0111-2","article-title":"Breast Cancer","volume":"5","author":"Harbeck","year":"2019","journal-title":"Nat. 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