Although enormous achievements have been made in targeted molecular therapies against hepatocellular carcinoma (HCC), the treatments can only prolong the life of patients with extrahepatic metastases. We evaluated thymoquinone (TQ), a compound from Nigella sativa Linn., for its anti-cancer effect on SK-Hep1 cells and HCC-xenograft nude mice. TQ effectively triggered cell death and activated p38 and extracellular signal-regulated kinases (Erk) pathways up to 24 h after treatment in cells. TQ-induced cell death was reversed by p38 inhibitor; however, it was enhanced by si-Erk. The caspase3 activation and TUNEL assay revealed a stronger toxic effect upon co-treatment with TQ and si-Erk. Our study suggested that phosphorylation of p38 in SK-Hep1 cells constituted the major factor leading to cell apoptosis, whereas phosphorylation of Erk led to drug resistance. Furthermore, TQ therapeutic effect was improved upon Erk inhibition in HCC-xenograft nude mice. TQ could present excellent anti-HCC potential under suitable p-Erk inhibiting conditions.

中文翻译：

---

Erk 磷酸化降低了人肝癌中百里醌的毒性

尽管针对肝细胞癌（HCC）的靶向分子治疗取得了巨大成就，但这些治疗只能延长肝外转移患者的生命。我们评估了百里醌 (TQ)，一种来自黑种草的化合物Linn.，因为其对 SK-Hep1 细胞和 HCC 异种移植裸鼠的抗癌作用。TQ 可有效触发细胞死亡并激活 p38 和细胞外信号调节激酶 (Erk) 通路，直至细胞处理后 24 小时。TQ 诱导的细胞死亡被 p38 抑制剂逆转；然而，它被 si-Erk 增强了。caspase3 激活和 TUNEL 测定显示在与 TQ 和 si-Erk 共同处理时具有更强的毒性作用。我们的研究表明 SK-Hep1 细胞中 p38 的磷酸化是导致细胞凋亡的主要因素，而 Erk 的磷酸化导致耐药性。此外，在 HCC 异种移植裸鼠中抑制 Erk 后 TQ 治疗效果得到改善。在合适的 p-Erk 抑制条件下，TQ 可以表现出优异的抗 HCC 潜力。