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夏至草醇通过诱导自噬性细胞死亡以及抑制癌细胞迁移和侵袭来抑制骨肉瘤癌细胞生长。

Marrubenol inhibits osteosarcoma cancer cell growth by inducing autophagic cell death and inhibiting cancer cell migration and invasion.

作者信息

Zhang Yu, Ma Renshi, Cheng Shihuan, Gu Guishan

机构信息

Department of Orthopedic Surgery, Changchun, Jilin, 130021, China.

出版信息

J BUON. 2018 May-Jun;23(3):729-734.

Abstract

PURPOSE

The present study aimed at evaluating the anticancer activity of marrubenol against osteosarcoma cells along with evaluating its effects on autophagic cell death, reactive oxygen species (ROS) generation and cell migration and invasion tendency.

METHODS

In this study the Saos-2 osteosarcoma cell line was used. Cell cytotoxicity effects were evaluated by MTT cell viability assay, while clonogenic assay assessed the effects on cancer cell colony formation. In vitro wound healing assay was used to evaluate the effects on cell migration. To confirm autophagy, we evaluated the expression of several autophagy-associated proteins Western blot assay along with transmission electron microscopy (TEM).

RESULTS

The results indicated that the marrubenol exhibited an IC50 value of 45 μM and exerted its cytotoxic effects in a dose-dependent manner. Moreover, it was observed that the drug inhibited colony formation and induced autophagy dose-dependently. The underlying mechanism for the induction of autophagy was found to be ROS-mediated and significant inhibition of cell migration as well as cell invasion potential of osteosarcoma cells at the IC50 was observed.

CONCLUSIONS

These results strongly indicate that marrubenol may be considered as a potent drug lead molecule for the treatment and management of osteosarcoma.

摘要

目的

本研究旨在评估夏至草醇对骨肉瘤细胞的抗癌活性,并评估其对自噬性细胞死亡、活性氧(ROS)生成以及细胞迁移和侵袭趋势的影响。

方法

本研究使用了Saos-2骨肉瘤细胞系。通过MTT细胞活力测定评估细胞毒性作用,而克隆形成试验评估对癌细胞集落形成的影响。体外伤口愈合试验用于评估对细胞迁移的影响。为了确认自噬,我们通过蛋白质免疫印迹法以及透射电子显微镜(TEM)评估了几种自噬相关蛋白的表达。

结果

结果表明,夏至草醇的IC50值为45 μM,并以剂量依赖方式发挥其细胞毒性作用。此外,观察到该药物剂量依赖性地抑制集落形成并诱导自噬。发现自噬诱导的潜在机制是ROS介导的,并且在IC50时观察到骨肉瘤细胞的细胞迁移以及细胞侵袭潜能受到显著抑制。

结论

这些结果强烈表明,夏至草醇可被视为治疗和管理骨肉瘤的一种有效的药物先导分子。

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