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Anti-hepatoma effect of taccalonolide A through suppression of sonic hedgehog pathway.
Artificial Cells, Nanomedicine, and Biotechnology ( IF 4.5 ) Pub Date : 2020-06-05 , DOI: 10.1080/21691401.2020.1773484
Hui Tian 1 , Zhenkun He 1
Affiliation  

Taccalonolide A has been reported to have anti-tumour efficiency. However, the underlying mechanism for taccalonolides A therapy of hepatocellular carcinoma (HCC) is still obscure. Cell viability was evaluated by cell counting kit-8 (CCK-8) assay. Apoptosis was determined by flow cytometry. Protein expression of B cell lymphoma (Bcl-2), Bcl-2 associated X (Bax), sonic hedgehog (Shh), Smoothened (Smo) and Gli family zinc finger 1 (Gli1) was analyzed by western blot. The expression of Shh, Smo and Gli1 mRNA was determined using quantitative real-time polymerase chain reaction (qRT-PCR). Results showed that taccalonolide A inhibited cell proliferation, induced apoptosis and cell cycle arrest at the G0/G1 phase, and improved the cytotoxicity of sorafenib in HCC cells. The expressions of Shh, Smo, Gli1 mRNA and protein were decreased after taccalonolide A treatment. More importantly, activation of the Shh pathway attenuated taccalonolide A-induced inhibition on cell viability and promotion on apoptosis and cell cycle arrest in HCC. Also, activation of the Shh pathway neutralized the effect of taccalonolide A on sorafenib cytotoxicity in HCC. We clarified that taccalonolide A suppressed cell viability facilitated apoptosis, and improved the cytotoxicity of sorafenib in HCC by inhibition of the activation of the Shh pathway, providing alternative treatments for HCC.

中文翻译:

他克洛奈德A的抗肝癌作用是通过抑制声波刺猬通路来实现的。

据报道他克洛奈德A具有抗肿瘤功效。但是,他克洛奈德A治疗肝细胞癌(HCC)的潜在机制仍然不清楚。通过细胞计数试剂盒8(CCK-8)分析评估细胞活力。通过流式细胞术确定细胞凋亡。B蛋白淋巴瘤(Bcl-2),Bcl-2相关X(Bax),声波刺猬(Shh),平滑化(Smo)和Gli家族锌指1(Gli1)的蛋白质表达通过蛋白质印迹分析。Shh,Smo和Gli1 mRNA的表达使用定量实时聚合酶链反应(qRT-PCR)确定。结果表明他克洛奈德A抑制细胞增殖,诱导细胞凋亡和细胞周期停滞在G0 / G1期,并改善索拉非尼在HCC细胞中的细胞毒性。Shh,Smo,他克洛奈德A治疗后Gli1 mRNA和蛋白均降低。更重要的是,Shh途径的激活减弱了他克洛奈德A诱导的HCC细胞活力抑制作用以及对细胞凋亡和细胞周期阻滞的促进作用。此外,Shh途径的激活中和了他卡洛奈德A对HCC中索拉非尼细胞毒性的影响。我们阐明,他克洛奈德A抑制细胞活力可促进细胞凋亡,并通过抑制Shh途径的活化来改善索拉非尼在HCC中的细胞毒性,从而为HCC提供替代治疗。Shh途径的激活中和了他卡洛奈德A对HCC中索拉非尼细胞毒性的影响。我们阐明,他克洛奈德A抑制细胞活力可促进细胞凋亡,并通过抑制Shh途径的活化来改善索拉非尼在HCC中的细胞毒性,从而为HCC提供替代治疗。Shh途径的激活中和了他卡洛奈德A对HCC中索拉非尼细胞毒性的影响。我们阐明,他克洛奈德A抑制细胞活力可促进细胞凋亡,并通过抑制Shh途径的活化来改善索拉非尼在HCC中的细胞毒性,从而为HCC提供替代治疗。
更新日期:2020-06-05
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