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：

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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。