转化生长因子-β1 (TGF-β1) 是一种免疫抑制细胞因子，在肺腺癌 (LUAD) 的肿瘤微环境 (TME) 中高表达。 TGF-β1在调节肿瘤转移和化疗耐药中发挥重要作用。然而，TGF-β1调节LUAD TAM顺铂耐药的具体分子机制仍不清楚。THP-1诱导的巨噬细胞与A549和H1975细胞共培养，随后转染沉默TGF-β1（siTGF-β1） 、GLI2 (siGLI2)、GLI2 过表达质粒及其阴性对照。通过 CCK-8 和集落形成测定来测量细胞活性。通过流式细胞术和TUNEL染色评估细胞凋亡。进行 Transwell 测定以评估细胞迁移和侵袭能力。通过qPCR、蛋白质印迹和免疫荧光方法评估Smad2/3、GLI2、细胞周期蛋白D和细胞周期蛋白E的表达水平。 ELISA法测定TGF-β1水平。巨噬细胞抑制LUAD细胞的凋亡，促进其迁移和侵袭。 TAM siTGF-β1 下调 Smad2/3 信号通路和 GLI2 表达，抑制细胞增殖并促进细胞凋亡。 SiGLI2 增加 LUAD 细胞系的凋亡并减少其增殖。 GLI2降低LUAD细胞的顺铂耐药性。TAM中TGF-β1的高表达通过Smad2/3途径正向激活GLI2的表达，进而调节cyclin D和cyclin E的表达，促进LUAD的顺铂耐药性。

Transforming growth factor-β1 (TGF-β1) is an immunosuppressive cytokine that is highly expressed in the tumor microenvironment (TME) of lung adenocarcinoma (LUAD). TGF-β1 plays important roles in regulating tumor metastasis and chemotherapy resistance. However, the specific molecular mechanisms by which TGF-β1 regulates cisplatin resistance in the TAM of LUAD remain unclear.THP-1 induced macrophages were co-cultured with A549 and H1975 cells, and subsequently transfected with silencing TGF-β1 (siTGF-β1), GLI2 (siGLI2), a GLI2 overexpression plasmid, and their negative controls. Cellular activity was measured by CCK-8 and colony formation assays. Cell apoptosis was evaluated by flow cytometry and TUNEL staining. Transwell assays were performed to assess cell migration and invasion capabilities. The levels of Smad2/3, GLI2, cyclin D, and cyclin E expression were evaluated by qPCR, western blotting, and immunofluorescence methods. TGF-β1 levels were determined by ELISA.Macrophages suppressed the apoptosis and promoted the migration and invasion of LUAD cells. TAM siTGF-β1 downregulated the Smad2/3 signaling pathways and GLI2 expression, deceased cell proliferation, and promoted apoptosis. SiGLI2 increased apoptosis and decreased the proliferation of LUAD cell lines. GLI2 decreased cisplatin resistance in LUAD cells.High expression of TGF-β1 in the TAM positively activates GLI2 expression via the Smad2/3 pathway, which subsequently regulates cyclin D and cyclin E expression, and promotes the cisplatin resistance of LUAD.