Department of Infectious Disease, Huaihe Hospital of Henan University, Kaifeng, Henan, China.
Artif Cells Nanomed Biotechnol. 2020 Dec;48(1):939-947. doi: 10.1080/21691401.2020.1773484.
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.
Taccalonolide A 已被报道具有抗肿瘤活性。然而，taccalonolides A 治疗肝细胞癌（HCC）的潜在机制仍不清楚。通过细胞计数试剂盒-8（CCK-8）测定评估细胞活力。通过流式细胞术测定细胞凋亡。通过 Western blot 分析 B 细胞淋巴瘤（Bcl-2）、Bcl-2 相关 X（Bax）、刺猬信号通路（Shh）、Smo 蛋白和 Gli 家族锌指蛋白 1（Gli1）的蛋白表达。使用实时定量聚合酶链反应（qRT-PCR）测定 Shh、Smo 和 Gli1 mRNA 的表达。结果表明，taccalonolide A 抑制细胞增殖，诱导 HCC 细胞凋亡和细胞周期停滞在 G0/G1 期，并提高索拉非尼的细胞毒性。taccalonolide A 处理后 Shh、Smo、Gli1 mRNA 和蛋白的表达降低。更重要的是，Shh 通路的激活减弱了 taccalonolide A 对细胞活力的抑制作用，促进了 HCC 细胞的凋亡和细胞周期停滞。此外，Shh 通路的激活中和了 taccalonolide A 对 HCC 中索拉非尼细胞毒性的作用。我们阐明了 taccalonolide A 通过抑制 Shh 通路的激活抑制细胞活力，促进 HCC 细胞凋亡，并提高索拉非尼的细胞毒性，为 HCC 提供了替代治疗方法。
