{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,7]],"date-time":"2025-06-07T11:10:04Z","timestamp":1749294604599,"version":"3.41.0"},"reference-count":0,"publisher":"Maad Rayan Publishing Company","content-domain":{"domain":["apb.tbzmed.ac.ir"],"crossmark-restriction":false},"short-container-title":["Adv Pharm Bull"],"abstract":"<jats:p>Purpose: The survival and progression of multiple myeloma (MM) cells rely heavily on supportive factors and cells within the MM microenvironment, notably macrophages. The PI3K signaling pathway plays a crucial role in both myeloma cells survival and macrophage polarity, making it a potential target for altering the MM microenvironment dynamics. Methods: In this study, the impact of LY294002, a PI3K signaling pathway inhibitor, on the viability of U266 myeloma cells in mono-culture and MM patient-derived bone marrow mononuclear cells (BM-MNCs) in co-culture was investigated. Additionally, the effect of treatments on the M1\/M2 macrophage ratio was assessed. Cultures were conducted in both two-dimensional (2D) matrix-free and fibrin gel-based three-dimensional (3D) environments. Results: The treatment significantly increased U266 cell death in 2D cultures, dose-dependently compared to control. However, this effect was not replicated in 3D cultures. In both 2D and 3D cultures, the percentages of cells in G0\/G1 phase were dose-dependently increased, compared to the untreated control. However, the percentages of cells in S and G2\/M phases in both 2D and 3D cultures were dose-dependently decreased, compared to control. Treatment of BM-MNCs with LY294002 showed patient- and culture-dependent patterns of CD138+ myeloma cell death and M1\/M2 macrophage ratio, contrasting the observed consistent responses in U266 mono-culture.Conclusion: LY294002 affected U266 cell viability and cell cycle in a dose-dependent manner in 2D mono-cultures. However, its impact varied in 3D cultures. Treatment of MNCs showed varied responses based on individuals and culture conditions, underscoring the need for more similar tumor microenvironment recapitulation for drug screening.<\/jats:p>","DOI":"10.34172\/apb.025.42774","type":"journal-article","created":{"date-parts":[[2025,4,26]],"date-time":"2025-04-26T08:53:33Z","timestamp":1745657613000},"update-policy":"https:\/\/doi.org\/10.34172\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["PI3K signaling pathway inhibitor affects myeloma cells in a culture-dependent manner"],"prefix":"10.34172","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-9139-6167","authenticated-orcid":true,"given":"Mehrnaz","family":"Janfada","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0223-9838","authenticated-orcid":true,"given":"Sadaf","family":"Vahdat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2213-8142","authenticated-orcid":true,"given":"Saeid","family":"Kaviani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"20123","published-online":{"date-parts":[[2025,4,24]]},"container-title":["Advanced Pharmaceutical Bulletin"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/apb.tbzmed.ac.ir\/Inpress\/apb-42774.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/apb.tbzmed.ac.ir\/Inpress\/apb-42774.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,7]],"date-time":"2025-06-07T10:31:17Z","timestamp":1749292277000},"score":1,"resource":{"primary":{"URL":"https:\/\/apb.tbzmed.ac.ir\/Inpress\/apb-42774"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,24]]},"references-count":0,"URL":"https:\/\/doi.org\/10.34172\/apb.025.42774","relation":{},"ISSN":["2228-5881","2251-7308"],"issn-type":[{"type":"print","value":"2228-5881"},{"type":"electronic","value":"2251-7308"}],"subject":[],"published":{"date-parts":[[2025,4,24]]},"assertion":[{"value":"Tabriz University of Medical Sciences","name":"journal_owner","label":"Journal Owner"},{"value":"Tabriz University of Medical Sciences","name":"journal_publisher","label":"Journal Publisher"},{"value":"2024-02-06","order":1,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}