OICC Press Progress in Biomaterials 2194-0517 15 1 2026 03 31 RNA-Seq Analysis Revealed the Suppressor Effects of Silybinin in Gastric and Breast Cancers Through the Downregulation of FGF and Wnt Signaling in Silybinin-Driven Modulation of ADSCs in Tumor Microenvironment 10.57647/pibm.2026.152603 EN Zahra Derakhshandeh Department of Biology, CT. C., Islamic Azad University, Tehran, Iran Keyvan Ansari Shiri Department of Biomedical Engineering, CT. C., Islamic Azad University, Tehran, Iran Soheila Zamanlui Benisi Department of Biomedical Engineering, CT. C., Islamic Azad University, Tehran, Iran Saeed Hesami Tackallou Department of Biology, CT. C., Islamic Azad University, Tehran, Iran Journal Article 2026 03 31 Adipose-derived mesenchymal stem cells (ADSCs) are key elements of the tumor microenvironment (TME), driving oncogenic advancement through paracrine signaling, epithelial-mesenchymal transition (EMT), and angiogenesis. Silybinin (SB), flavonoid from Silybum marianum, illustrated anticancer potential; however, impacts on ADSCs in breast and gastric cancers remain poorly understood. Human (ADSCs) treated with various SB concentration, and viability was assessed by MTT assay to detect the optimum dose. Gene expression profiling was performed by RNA-sequencing (Illumina HiSeq 4000). Differentially expressed genes (DEGs) were detected using HISAT2 and NOISeq (log2|FC| ≥ 1, p ≤ 0.05, and FDR ≤ 0.1), followed by KEGG enrichment analysis and qRT-PCR validation. 1-  MTT assay demonstrated low-dose SB (0.005-0.5 pg) increased ADSCs viability (p < 0.01), while higher doses (10-50 pg) induced cytotoxicity (p < 0.05); 0.5 pg was optimal. 2- SB modulated expression of 324 genes (210 downregulated, 114 upregulated), enriching breast and gastric cancer pathways. Four oncogenic genes, FGF1, FGF5, FGF18, and TCF7 were downregulated, regulators of FGF-FGFR and Wnt/β-catenin signaling sustaining tumor growth, metastasis, and EMT. 3- qRT-PCR confirmed these findings (P < 0.05). Downregulation of FGF1, FGF5, and FGF18 inhibits proliferative and angiogenic signaling, while reduced TCF7 suppresses Wnt-driven stemness, promoting apoptosis. Silybinin reprograms ADSCs within the TME by downregulating FGF1, FGF5, FGF18, and TCF7, key drivers of FGF-FGFR and Wnt/β-catenin-mediated tumor progression, reducing ADSC-mediated tumor support, increasing apoptosis, positioning it as a candidate for disrupting ADSC-cancer crosstalk.