{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T02:28:24Z","timestamp":1790994504696,"version":"4.1.0"},"reference-count":74,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T00:00:00Z","timestamp":1705622400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Network for Canadian Oral Health and Research (NCOHR)","award":["NGH-154223"],"award-info":[{"award-number":["NGH-154223"]}]},{"name":"the Network for Canadian Oral Health and Research (NCOHR)","award":["RSPD2024R552"],"award-info":[{"award-number":["RSPD2024R552"]}]},{"name":"the Researchers Supporting Project","award":["NGH-154223"],"award-info":[{"award-number":["NGH-154223"]}]},{"name":"the Researchers Supporting Project","award":["RSPD2024R552"],"award-info":[{"award-number":["RSPD2024R552"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Oral cancer is considered as one of the most common malignancies worldwide. Its conventional treatment primarily involves surgery with or without postoperative adjuvant therapy. The targeting of signaling pathways implicated in tumorigenesis is becoming increasingly prevalent in the development of new anticancer drug candidates. Based on our recently published data, Rapamycin, an inhibitor of the mTOR pathway, exhibits selective antitumor activity in oral cancer by inhibiting cell proliferation and inducing cancer cell apoptosis, autophagy, and cellular stress. In the present study, our focus is on elucidating the genetic determinants of Rapamycin\u2019s action and the interaction networks accountable for tumorigenesis suppression. To achieve this, gingival carcinoma cell lines (Ca9-22) were exposed to Rapamycin at IC50 (10 \u00b5M) for 24 h. Subsequently, we investigated the genetic profiles related to the cell cycle, apoptosis, and autophagy, as well as gene\u2013gene interactions, using QPCR arrays and the Gene MANIA website. Overall, our results showed that Rapamycin at 10 \u00b5M significantly inhibits the growth of Ca9-22 cells after 24 h of treatment by around 50% by suppression of key modulators in the G2\/M transition, namely, Survivin and CDK5RAP1. The combination of Rapamycin with Cisplatin potentializes the inhibition of Ca9-22 cell proliferation. A P1\/Annexin-V assay was performed to evaluate the effect of Rapamycin on cell apoptosis. The results obtained confirm our previous findings in which Rapamycin at 10 \u03bcM induces a strong apoptosis of Ca9-22 cells. The live cells decreased, and the late apoptotic cells increased when the cells were treated by Rapamycin. To identify the genes responsible for cell apoptosis induced by Rapamycin, we performed the RT2 Profiler PCR Arrays for 84 apoptotic genes. The blocked cells were believed to be directed towards cell death, confirmed by the downregulation of apoptosis inhibitors involved in both the extrinsic and intrinsic pathways, including BIRC5, BNIP3, CD40LG, DAPK1, LTA, TNFRSF21 and TP73. The observed effects of Rapamycin on tumor suppression are likely to involve the autophagy process, evidenced by the inhibition of autophagy modulators (TGF\u03b21, RGS19 and AKT1), autophagosome biogenesis components (AMBRA1, ATG9B and TMEM74) and autophagy byproducts (APP). Identifying gene\u2013gene interaction (GGI) networks provided a comprehensive view of the drug\u2019s mechanism and connected the studied tumorigenesis processes to potential functional interactions of various kinds (physical interaction, co-expression, genetic interactions etc.). In conclusion, Rapamycin shows promise as a clinical agent for managing Ca9-22 gingiva carcinoma cells.<\/jats:p>","DOI":"10.3390\/ph17010131","type":"journal-article","created":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T03:33:41Z","timestamp":1705635221000},"page":"131","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Rapamycin as a Potential Alternative Drug for Squamous Cell Gingiva Carcinoma (Ca9-22): A Focus on Cell Cycle, Apoptosis and Autophagy Genetic Profile"],"prefix":"10.3390","volume":"17","author":[{"given":"Sofia","family":"Papadakos","sequence":"first","affiliation":[{"name":"Groupe de Recherche en \u00c9cologie Buccale, Facult\u00e9 de M\u00e9decine Dentaire, Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0716-8215","authenticated-orcid":false,"given":"Hawraa","family":"Issa","sequence":"additional","affiliation":[{"name":"Groupe de Recherche en \u00c9cologie Buccale, Facult\u00e9 de M\u00e9decine Dentaire, Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3942-5455","authenticated-orcid":false,"given":"Abdulaziz","family":"Alamri","sequence":"additional","affiliation":[{"name":"Biochemistry Department, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3045-1350","authenticated-orcid":false,"given":"Abdullah","family":"Alamri","sequence":"additional","affiliation":[{"name":"Biochemistry Department, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1643-0377","authenticated-orcid":false,"given":"Abdelhabib","family":"Semlali","sequence":"additional","affiliation":[{"name":"Groupe de Recherche en \u00c9cologie Buccale, Facult\u00e9 de M\u00e9decine Dentaire, Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,19]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2022). 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