Department of Ultrasound, The First Affiliated Hospital of Yangtze University, Jingzhou City, P. R.China.
Int J Hyperthermia. 2024;41(1):2359496. doi: 10.1080/02656736.2024.2359496. Epub 2024 Jun 23.
Microwave ablation (MWA) is a widely adopted treatment technique for hepatocellular carcinoma (HCC). However, MWA alone is of limited use and has a high recurrence rate. Transforming growth factor-β1 (TGF-β1) is recognized as a potential therapeutic target for HCC patients. Therefore, this study was designed to investigate whether the TGF-β1 inhibitor could increase the efficacy of MWA therapy for HCC treatment.
In vitro, HCC cells challenged with TGF-β1 inhibitor (SB-525334), or normal saline were then heated by microwave. Methyl tetrazolium assays were performed to detect cell survival rate and half-maximal drug inhibitory concentration (IC50). Cell viability and apoptosis were detected by cell counting kit-8 assays, flow cytometry and western blotting. In vivo, the mice injected with HepG2 cells received oral gavage of SB-525334 (20 mg/kg) or normal saline and MWA at a power of 15 W. Tumor volume was recorded. Expression of Ki67 and apoptosis-related proteins were detected by immunohistochemistry and western blotting. TUNEL assays were used to detect cell death ratio. Histopathological changes were examined by hematoxylin and eosin staining. The mechanisms associated with the function of MWA combined with TGF-β1 inhibitor in HCC development were explored by western blotting.
Combination of MWA and SB-525334 decreased the survival rate and promoted the apoptosis of HCC cells compared with MWA alone. SB-525334 enhanced the suppressive effect of MWA on tumor growth and amplified cell apoptosis. Mechanistically, MWA collaborated with SB-525334 inhibitor inactivated the TGF-β1/Smad2/Smad3 pathway.
TGF-β1 inhibitor enhances the therapeutic effect of MWA on HCC.
微波消融（MWA）是治疗肝细胞癌（HCC）的一种广泛应用的治疗技术。然而，MWA 单独使用效果有限，复发率高。转化生长因子-β1（TGF-β1）被认为是 HCC 患者的潜在治疗靶点。因此，本研究旨在探讨 TGF-β1 抑制剂是否可以提高 MWA 治疗 HCC 的疗效。
在体外，用 TGF-β1 抑制剂（SB-525334）或生理盐水处理 HCC 细胞，然后用微波加热。采用甲基噻唑基四唑法检测细胞存活率和半最大药物抑制浓度（IC50）。通过细胞计数试剂盒-8 法、流式细胞术和 Western blot 检测细胞活力和细胞凋亡。在体内，将 HepG2 细胞注射到小鼠体内，然后给予 SB-525334（20mg/kg）或生理盐水口服灌胃和 15W 的 MWA。记录肿瘤体积。通过免疫组化和 Western blot 检测 Ki67 和凋亡相关蛋白的表达。TUNEL 检测法检测细胞死亡比例。通过苏木精和伊红染色观察组织病理学变化。Western blot 法探讨 MWA 联合 TGF-β1 抑制剂在 HCC 发展中的作用机制。
与单独 MWA 相比，MWA 联合 SB-525334 降低了 HCC 细胞的存活率并促进了细胞凋亡。SB-525334 增强了 MWA 对肿瘤生长的抑制作用并放大了细胞凋亡。机制上，MWA 与 SB-525334 抑制剂协同作用，使 TGF-β1/Smad2/Smad3 通路失活。
TGF-β1 抑制剂增强了 MWA 治疗 HCC 的疗效。
