TGF-β1 inhibitor enhances the therapeutic effect of microwave ablation on hepatocellular carcinoma.

IF 3 3区 医学 Q2 ONCOLOGY International Journal of Hyperthermia Pub Date : 2024-01-01 Epub Date: 2024-06-23 DOI:10.1080/02656736.2024.2359496
Shufang Xiang, Juan Li, Mei Zhang
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Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: TGF-β1 inhibitor enhances the therapeutic effect of MWA on HCC.

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TGF-β1抑制剂可增强微波消融对肝细胞癌的治疗效果
背景:微波消融(MWA)是一种广泛采用的肝细胞癌(HCC)治疗技术。然而,单用微波消融术的作用有限,而且复发率较高。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 抑制剂能否提高 MWA 治疗 HCC 的疗效:方法: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。用甲基四氮唑试验检测细胞存活率和半最大药物抑制浓度(IC50)。细胞活力和细胞凋亡通过细胞计数试剂盒-8测定法、流式细胞术和免疫印迹法进行检测。在体内,注射 HepG2 细胞的小鼠口服 SB-525334(20 毫克/千克)或生理盐水和功率为 15 瓦的 MWA。记录肿瘤体积。通过免疫组化和免疫印迹检测 Ki67 和凋亡相关蛋白的表达。TUNEL检测法用于检测细胞死亡比率。组织病理学变化通过苏木精和伊红染色进行检测。通过免疫印迹法探讨了 MWA 与 TGF-β1 抑制剂联合作用于 HCC 的相关机制:结果:与单独使用 MWA 相比,MWA 与 SB-525334 联合使用可降低 HCC 细胞的存活率并促进其凋亡。SB-525334增强了MWA对肿瘤生长的抑制作用,并扩大了细胞凋亡。从机理上讲,MWA与SB-525334抑制剂共同作用,使TGF-β1/Smad2/Smad3通路失活:结论:TGF-β1 抑制剂增强了 MWA 对 HCC 的治疗效果。
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来源期刊
CiteScore
5.90
自引率
12.90%
发文量
153
审稿时长
6-12 weeks
期刊介绍: The International Journal of Hyperthermia
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