{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T04:30:16Z","timestamp":1786681816895,"version":"build-2736575974"},"reference-count":46,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003141","name":"Secretar\u00eda de Ciencia, Humanidades, Tecnolog\u00eda e Innovaci\u00f3n","doi-asserted-by":"crossref","award":["1277373"],"award-info":[{"award-number":["1277373"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003141","name":"Secretar\u00eda de Ciencia, Humanidades, Tecnolog\u00eda e Innovaci\u00f3n","doi-asserted-by":"crossref","award":["1031018"],"award-info":[{"award-number":["1031018"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"crossref"}]},{"award":["1277373"],"award-info":[{"award-number":["1277373"]}],"id":[{"id":"https:\/\/ror.org\/059ex5q34","id-type":"ROR","asserted-by":"publisher"}]},{"award":["1031018"],"award-info":[{"award-number":["1031018"]}],"id":[{"id":"https:\/\/ror.org\/059ex5q34","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Cervical cancer (CC) is the most clinically significant HPV-associated malignancy. Platinum-based chemotherapies produce drug resistance and serious adverse effects. Drug repurposing and combinations are promising approaches to improve the antitumor response. Here, we evaluated the antineoplastic potential of loratadine and simvastatin alone and in combination with cisplatin and gefitinib in HPV-positive CC cells. Methods: HeLa and SiHa CC cells were treated with loratadine, simvastatin, cisplatin, gefitinib, or their combinations. Metabolic activity was assessed using the MTT assay to determine drug inhibitory concentrations (IC20, IC50) from concentration\u2013response curves. Apoptosis was assessed by Annexin V-FITC\/PI flow cytometry. Clonogenic survival and migratory capacity were evaluated using colony formation and wound-healing assays, respectively. Tumor formation was evaluated in vivo using the chick chorioallantoic membrane model. Results: Metabolic activity decreased in a concentration-dependent manner following drug treatment in both cell lines. Several combination regimens at IC20 significantly improved reductions in metabolic activity and increases in apoptosis compared with monotherapies or two-drug combinations. Notably, some three-drug combinations, with or without cisplatin, had similar effects to the quadruple regimen. Combination treatments also reduced clonogenic survival and migratory capacity, as well as tumor formation and cancer cell dissemination in vivo. Conclusions: Drug combinations at relatively low concentrations (IC20) significantly enhanced the anticancer effects on CC cells in in vitro and in vivo settings. These findings support the potential of drug repurposing and combination strategies as promising approaches to decrease adverse side effects while improving therapeutic efficacy for the benefit of CC patients.<\/jats:p>","DOI":"10.3390\/cancers18162589","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T07:57:26Z","timestamp":1786521446000},"page":"2589","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Antineoplastic Activity of the Combination Loratadine\u2013Simvastatin\u2013Gefitinib in HPV-Positive Cervical Cancer Cells: In Vitro and In Vivo Studies"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1114-0348","authenticated-orcid":false,"given":"Tania","family":"Raya-Bahena","sequence":"first","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Centro de Investigaci\u00f3n y de Estudios Avanzados del Instituto Polit\u00e9cnico Nacional, Av. IPN 2508, Mexico City 07360, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rene M.","family":"Rivera-Escobar","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Centro de Investigaci\u00f3n y de Estudios Avanzados del Instituto Polit\u00e9cnico Nacional, Av. IPN 2508, Mexico City 07360, Mexico"},{"name":"Department of Biology of Reproduction, Biological Sciences and Health Division (DCBS), Autonomous Metropolitan University (UAM), Mexico City 09310, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Hern\u00e1ndez-Gallegos","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Centro de Investigaci\u00f3n y de Estudios Avanzados del Instituto Polit\u00e9cnico Nacional, Av. IPN 2508, Mexico City 07360, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1421-3720","authenticated-orcid":false,"given":"Javier E.","family":"Jim\u00e9nez-Salazar","sequence":"additional","affiliation":[{"name":"Department of Biology of Reproduction, Biological Sciences and Health Division (DCBS), Autonomous Metropolitan University (UAM), Mexico City 09310, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4815-2516","authenticated-orcid":false,"given":"Pablo","family":"Dami\u00e1n-Matsumura","sequence":"additional","affiliation":[{"name":"Department of Biology of Reproduction, Biological Sciences and Health Division (DCBS), Autonomous Metropolitan University (UAM), Mexico City 09310, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3311-2258","authenticated-orcid":false,"given":"Janice","family":"Garc\u00eda-Quiroz","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda de La Reproducci\u00f3n Dr. Carlos Gual Castro, Instituto Nacional de Ciencias M\u00e9dicas y Nutrici\u00f3n Salvador Zubir\u00e1n, Av. Vasco de Quiroga No. 15, Belisario Dom\u00ednguez Secci\u00f3n XVI, Tlalpan, Mexico City 14080, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8886-086X","authenticated-orcid":false,"given":"Javier","family":"Camacho","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Centro de Investigaci\u00f3n y de Estudios Avanzados del Instituto Polit\u00e9cnico Nacional, Av. IPN 2508, Mexico City 07360, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Meng, X., Yang, B., Yin, H., Chen, J., Ma, W., Xu, Z., and Shen, Y. (2025). Global Burden and Incidence Trends in Cancers Associated with Human Papillomavirus Infection: A Population-Based Systematic Study. 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