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用海蓬子乙酸乙酯提取物处理肝癌细胞,可以减少索拉非尼的剂量和毒性,同时保持其疗效。

Treatment of liver cancer cells with ethyl acetate extract of Crithmum maritimum permits reducing sorafenib dose and toxicity maintaining its efficacy.

机构信息

Interdisciplinary Department of Medicine, University of Bari School of Medicine, Bari, Italy.

International Centre for Advanced Mediterranean Agronomic Studies - CHIEAM, Valenzano (BA), Italy.

出版信息

J Pharm Pharmacol. 2021 Sep 7;73(10):1369-1376. doi: 10.1093/jpp/rgab070.

Abstract

OBJECTIVES

Hepatocellular carcinoma (HCC) is one of the most frequent tumours worldwide and available drugs are inadequate for therapeutic results and tolerability. Hence, novel effective therapeutic tools with fewer side effects are of paramount importance. We have previously shown that Crithmum maritimum ethyl acetate extract exerts a cytostatic effect in HCC cells. Here, we tested whether C. maritimum ethyl acetate extract in combination with half sorafenib IC50 dose ameliorated efficacy and toxicity of sorafenib in inhibiting liver cancer cell growth. Moreover, we investigated the mechanisms involved.

METHODS

Two HCC cell lines (Huh7 and HepG2) were treated with C. maritimum ethyl acetate extract and half IC50 sorafenib dose usually employed in vitro. Then, cell proliferation, growth kinetics and cell toxicity were analysed together with an investigation of the cellular mechanisms involved, focusing on cell cycle regulation and apoptosis.

KEY FINDINGS

Results show that combined treatment with C. maritimum ethyl acetate extract and half IC50 sorafenib dose decreased cell proliferation comparably to full-dose sorafenib without increasing cell toxicity as confirmed by the effect on cell cycle regulation and apoptosis.

CONCLUSIONS

These results provide scientific support for the possibility of an effective integrative therapeutic approach for HCC with fewer side effects on patients.

摘要

目的

肝细胞癌(HCC)是全球最常见的肿瘤之一,可用的药物在治疗效果和耐受性方面都不理想。因此,具有更少副作用的新型有效治疗工具至关重要。我们之前已经表明,海蓬子乙酸乙酯提取物在 HCC 细胞中具有细胞抑制作用。在这里,我们测试了海蓬子乙酸乙酯提取物与半剂量索拉非尼联合使用是否能改善索拉非尼抑制肝癌细胞生长的疗效和毒性。此外,我们还研究了相关的作用机制。

方法

用海蓬子乙酸乙酯提取物和通常在体外使用的半 IC50 索拉非尼剂量处理两种 HCC 细胞系(Huh7 和 HepG2)。然后,分析细胞增殖、生长动力学和细胞毒性,并研究相关的细胞机制,重点关注细胞周期调控和细胞凋亡。

主要发现

结果表明,与全剂量索拉非尼相比,海蓬子乙酸乙酯提取物与半 IC50 索拉非尼剂量联合治疗可降低细胞增殖,而不会增加细胞毒性,这可以通过对细胞周期调控和细胞凋亡的影响得到证实。

结论

这些结果为 HCC 进行有效、副作用更小的综合治疗方法提供了科学依据。

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