Department of Urology Surgery, Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine, Hangzhou, China.
Urol Int. 2023;107(9):848-856. doi: 10.1159/000532128. Epub 2023 Sep 4.
The aim of the study was to investigate the potential mechanism of specificity protein 1 (SP1) in bladder cancer progression through the PTEN-mediated AKT/mTOR pathway.
Human bladder cancer cell lines (HT-1197, HT-1376, and T24) and normal ureteral epithelial cell line SV-HUC-1 were used. SP1 expression was detected via quantitative real-time PCR and Western blotting. Cell viability, migration, invasion, and apoptosis were assessed using CCK-8, transwell, and flow cytometry assays, respectively. The involvement of the PTEN-mediated AKT/mTOR pathway was evaluated by Western blot. A mouse xenograft model was built, and immunohistochemical staining was applied to visualize SP1 and Ki67 expression in tumor tissues.
SP1 was overexpressed in bladder cancer cells. SP1 knockdown inhibited viability, migration, and invasion and promoted apoptosis in bladder cancer cells. PTEN intervention increased cell viability, migration, and invasion and decreased apoptosis, which was reversed by SP1 knockdown. The activation of the AKT/mTOR pathway resulting from PTEN knockdown was attenuated by SP1 knockdown. In vivo results showed that SP1 knockdown suppressed tumor growth, increased PTEN expression, and decreased AKT/mTOR pathway-related protein levels.
SP1 promotes bladder cancer progression by inhibiting the PTEN-mediated AKT/mTOR pathway. Targeting SP1 may be a potential therapeutic strategy for treating bladder cancer.
本研究旨在通过 PTEN 介导的 AKT/mTOR 通路探究特异性蛋白 1（SP1）在膀胱癌进展中的潜在作用机制。
采用人膀胱癌细胞系（HT-1197、HT-1376 和 T24）和正常输尿管上皮细胞系 SV-HUC-1。通过实时定量 PCR 和 Western blot 检测 SP1 表达。使用 CCK-8、Transwell 和流式细胞术分别评估细胞活力、迁移、侵袭和凋亡。通过 Western blot 评估 PTEN 介导的 AKT/mTOR 通路的参与情况。构建小鼠异种移植模型，并应用免疫组织化学染色来可视化肿瘤组织中 SP1 和 Ki67 的表达。
SP1 在膀胱癌细胞中过表达。SP1 敲低抑制膀胱癌细胞活力、迁移和侵袭，促进细胞凋亡。PTEN 干预增加细胞活力、迁移和侵袭，减少细胞凋亡，而 SP1 敲低可逆转这种作用。PTEN 敲低导致的 AKT/mTOR 通路的激活被 SP1 敲低所抑制。体内结果表明，SP1 敲低抑制肿瘤生长，增加 PTEN 表达，并降低 AKT/mTOR 通路相关蛋白水平。
SP1 通过抑制 PTEN 介导的 AKT/mTOR 通路促进膀胱癌的进展。靶向 SP1 可能是治疗膀胱癌的一种潜在治疗策略。
