{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T13:17:12Z","timestamp":1773667032088,"version":"3.50.1"},"reference-count":36,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010798","name":"Sunway University Early Career Research Grant Scheme","doi-asserted-by":"publisher","award":["GRTIN-ECR-SBMDC-05-2024"],"award-info":[{"award-number":["GRTIN-ECR-SBMDC-05-2024"]}],"id":[{"id":"10.13039\/501100010798","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010798","name":"Sunway University Research Accelerator Grant Scheme","doi-asserted-by":"publisher","award":["GRTIN-RAG-SBMDC-05-2025"],"award-info":[{"award-number":["GRTIN-RAG-SBMDC-05-2025"]}],"id":[{"id":"10.13039\/501100010798","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MPs"],"abstract":"<jats:p>Three-dimensional (3D) spheroid cancer models provide enhanced physiological relevance relative to traditional monolayer cultures but often demonstrate restricted drug responsiveness due to their dense architecture, hypoxic gradients, and diminished therapeutic penetrance. This study overcomes these limitations by establishing a sensitized 3D spheroid cancer cell model that employs the adenovirus-mediated gene expressions of tumor-suppressor and pro-apoptotic genes consisting of MOAP-1, BAX, and RASSF1A. The optimization of adenoviral infectivity led to the discovery of an intermediate multiplicity of infection (MOI) that facilitated effective and uniform transduction while reducing cytotoxicity. Adenovirus-infected 3D spheroid cells demonstrated enhanced apoptotic activities, evidenced by increased cell death relative to untreated spheroids. When exposed to the anti-cancer compound such as piperonal and pyrazole, the sensitized spheroids exhibited significantly enhanced drug responsiveness and synergistic effects over a five-day treatment period, surpassing the effects of adenovirus or anti-cancer drug treatment alone. Notably, similar responses were noted between low- and high drug doses, suggesting an enhancement of therapeutic efficacy at lower concentrations. This sensitized 3D spheroid model constitutes a more predictive in vitro system for anti-cancer drug discovery, facilitating enhanced mechanistic evaluation and the identification of potent drug candidates with greater translational significance.<\/jats:p>","DOI":"10.3390\/mps9020049","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T11:13:14Z","timestamp":1773659594000},"page":"49","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Establishment of a Sensitized 3D Spheroid Cancer Cell Model for Enhanced Anti-Cancer Drug Discovery"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2106-1449","authenticated-orcid":false,"given":"Ee Wern","family":"Tan","sequence":"first","affiliation":[{"name":"Sunway Biofunctional Molecules Discovery Centre, Faculty of Medical and Life Sciences, Sunway University, Sunway City 47500, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tien Yang","family":"Goh","sequence":"additional","affiliation":[{"name":"Sunway Biofunctional Molecules Discovery Centre, Faculty of Medical and Life Sciences, Sunway University, Sunway City 47500, Malaysia"},{"name":"Department of Biological Sciences, Faculty of Science, National University of Singapore, 21 Lower Kent Ridge Rd, University Hall, Singapore 119077, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shi Hui","family":"Law","sequence":"additional","affiliation":[{"name":"Sunway Biofunctional Molecules Discovery Centre, Faculty of Medical and Life Sciences, Sunway University, Sunway City 47500, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kuan Onn","family":"Tan","sequence":"additional","affiliation":[{"name":"Sunway Biofunctional Molecules Discovery Centre, Faculty of Medical and Life Sciences, Sunway University, Sunway City 47500, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bey Hing","family":"Goh","sequence":"additional","affiliation":[{"name":"Sunway Biofunctional Molecules Discovery Centre, Faculty of Medical and Life Sciences, Sunway University, Sunway City 47500, Malaysia"},{"name":"Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW 2007, Australia"},{"name":"Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Habanjar, O., Diab-Assaf, M., Caldefie-Chezet, F., and Delort, L. 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