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丹参中提取的隐丹参酮对卵巢癌细胞的体外抗肿瘤及化疗增敏作用

Anti-tumor and chemosensitization effects of Cryptotanshinone extracted from Salvia miltiorrhiza Bge. on ovarian cancer cells in vitro.

作者信息

Jiang Guoqiang, Liu Jia, Ren Baoyin, Zhang Lin, Owusu Lawrence, Liu Likun, Zhang Jing, Tang Yawei, Li Weiling

机构信息

Department of Biotechnology, Dalian Medical University, Dalian 116044, Liaoning, China.

Department of Integrative Medicine, Dalian Medical University, Dalian 116044, Liaoning, China; Department of Biochemistry and Biotechnology, Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana.

出版信息

J Ethnopharmacol. 2017 Jun 9;205:33-40. doi: 10.1016/j.jep.2017.04.026. Epub 2017 Apr 27.

DOI:10.1016/j.jep.2017.04.026
PMID:28456578
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Cryptotanshinone, a natural compound isolated from the roots of Salvia miltiorrhiza Bge. (Danshen), is a commonly used traditional Chinese medicine to treat high blood pressure in some countries. It has been shown that Cryptotanshinone induces cancer cells apoptosis and impairs cell migration and invasion. However, the antiproliferation and chemosensitization effects of Cryptotanshinone on ovarian cancer and the underlying mechanism are not fully elucidated.

AIM OF STUDY

In this study, we evaluated the inhibitory effect of Cryptotanshinone on ovarian cancer cells and explored the underlying molecular mechanism. Additionally, the chemosensitization potential of Cryptotanshinone was evaluated in combination with cisplatin.

MATERIALS AND METHODS

MTT assay was used for cell viability assessment of ovarian cancer A2780 cells treated with Cryptotanshinone and/ or cisplatin. Flow cytometry was used for apoptosis analysis. Wound healing and transwell assays were used for migratory and invasive potential assessment of Cryptotanshinone-treated ovarian cancer cells. Western blot was used to investigate proteins involved in the mechanisms for metastasis and apoptosis. γH2AX immunocytochemistry was used to detect DNA damage in A2780 cells exposed to Cryptotanshinone and/or cisplatin.

RESULTS

Cryptotanshinone significantly induced ovarian cancer A2780 cells apoptosis by activating caspase cascade. Additionally, wound healing and transwell assays revealed that Cryptotanshinone could suppress migration and invasion of ovarian cancer cells and dramatically inhibited MMP-2 and MMP-9 expression. Furthermore, Cryptotanshinone could sensitize A2780 cells to cisplatin treatment in a dose-dependent manner.

CONCLUSION

Our data confirmed the anti-tumor effect of Cryptotanshinone on ovarian cancer cells and provided new findings that Cryptotanshinone could sensitize ovarian cancer cells to chemotherapy.

摘要

民族药理学相关性

隐丹参酮是从丹参(Salvia miltiorrhiza Bge.)根中分离出的一种天然化合物,在一些国家是治疗高血压的常用中药。研究表明,隐丹参酮可诱导癌细胞凋亡,并抑制细胞迁移和侵袭。然而,隐丹参酮对卵巢癌的抗增殖和化学增敏作用及其潜在机制尚未完全阐明。

研究目的

本研究评估了隐丹参酮对卵巢癌细胞的抑制作用,并探讨了其潜在的分子机制。此外,还评估了隐丹参酮与顺铂联合使用时的化学增敏潜力。

材料与方法

采用MTT法评估经隐丹参酮和/或顺铂处理的卵巢癌A2780细胞的活力。采用流式细胞术进行凋亡分析。采用伤口愈合实验和Transwell实验评估经隐丹参酮处理的卵巢癌细胞的迁移和侵袭能力。采用蛋白质免疫印迹法研究参与转移和凋亡机制的蛋白质。采用γH2AX免疫细胞化学法检测暴露于隐丹参酮和/或顺铂的A2780细胞中的DNA损伤。

结果

隐丹参酮通过激活半胱天冬酶级联反应显著诱导卵巢癌A2780细胞凋亡。此外,伤口愈合实验和Transwell实验表明,隐丹参酮可抑制卵巢癌细胞的迁移和侵袭,并显著抑制MMP-2和MMP-9的表达。此外,隐丹参酮可使A2780细胞对顺铂治疗产生剂量依赖性的增敏作用。

结论

我们的数据证实了隐丹参酮对卵巢癌细胞的抗肿瘤作用,并提供了新的发现,即隐丹参酮可使卵巢癌细胞对化疗产生增敏作用。

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