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Cisplatin (CDDP) is the major drug that has been extremely used in all stages in treating CC, although relapse and malignant instances have been observed as a result of cisplatin resistance in CC. In the present study, we established Cisplatin resistant CC HeLa cell line model and the cytotoxic effects of Andro as a single agent or in combination with CDDP were investigated to assess its potential as a chemotherapeutic agent in cisplatin\u2010resistant HeLa (CisR\u2010HeLa) cells. Andro enhanced the cytotoxicity of CDDP in CisR\u2010HeLa cells and shown a synergistic effect by reducing cell viability, proliferation, migration, invasion, and inducing apoptosis in cisplatin resistant cells. Furthermore, we evaluated the expression levels of inflammatory and oncogenic proteins, SPP1, NF\u2010kB, iNOS, COX\u20102, and the PI3K\/AKT signaling pathway, which are associated with cisplatin resistance, as well as using Andro to regulate the targeted markers in CisR\u2010HeLa cells to overcome resistance. The results show that suppressing SPP1 and NF\u2010kB by Andro alone or in combination with CDDP regulates iNOS, COX\u20102, and increases PTEN expression. The addition of Andro to CDDP inhibited PI3K and AKT expression as well as triggered synergistic apoptosis, which could be associated with variations in Bax and Bcl\u20102 protein levels. The results suggest that Andro in combination with CDDP exhibits synergistic anti\u2010tumor growth efficacy that targets multiple inflammatory markers, resulting in a promising treatment option for individuals with recurrent cancer due to drug resistance and advanced CC.<\/jats:p>","DOI":"10.1002\/ddr.70052","type":"journal-article","created":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T09:46:32Z","timestamp":1738230392000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Andrographolide Mitigates Cisplatin Resistance by Inhibiting SPP1 Regulated NF\u2010kB\/iNOS\/COX\u20102 and PI3K\/AKT Pathway in Cisplatin Resistant Cervical Carcinoma Cells"],"prefix":"10.1002","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7317-4800","authenticated-orcid":false,"given":"Akbar","family":"Pasha","sequence":"first","affiliation":[{"name":"Department of Genetics &amp; Biotechnology University College of Science, Osmania University Hyderabad Telangana India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doneti","family":"Ravinder","sequence":"additional","affiliation":[{"name":"Department of Genetics &amp; Biotechnology University College of Science, Osmania University Hyderabad Telangana India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Smita C.","family":"Pawar","sequence":"additional","affiliation":[{"name":"Department of Genetics &amp; Biotechnology University College of Science, Osmania University Hyderabad Telangana India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,30]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2010.01115.x"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21207613"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2010.08.010"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aohep.2020.01.001"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/1099-1573(200008)14:5<333::AID-PTR584>3.0.CO;2-D"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v18.i30.3923"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.3113"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2013.08.041"},{"key":"e_1_2_12_10_1","first-page":"308","article-title":"Andrographolide, a Novel NF\u2010\u03baB Inhibitor, Inhibits Vascular Smooth Muscle Cell Proliferation and Cerebral Endothelial Cell Inflammation","volume":"30","author":"Chang C. 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