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首页> 外文期刊>Cellular Physiology and Biochemistry >Emodin: One Main Ingredient of Shufeng Jiedu Capsule Reverses Chemoresistance of Lung Cancer Cells Through Inhibition of EMT
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Emodin: One Main Ingredient of Shufeng Jiedu Capsule Reverses Chemoresistance of Lung Cancer Cells Through Inhibition of EMT

机译:大黄素:舒风解毒胶囊的一种主要成分通过抑制EMT逆转肺癌细胞的化学耐药性。

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>Background: Chemoresistance has become a an important worldwide problem to cancer treatment. Understanding the mechanism of drug resistance is the key to solve this problem and improve the survival of the patient. Doxorubicin and its analogues are widely used as antitumor drugs but many doxorubicin resistant cases have been identified in recent years. Doxorubicin (Dox) resistance is a very serious phenomenon in lung cancer treatment. As we could show previously, Shufeng Jiedu Capsule (SFJDC) can effectively reverse H69AR cells resistance to Dox, thus, the present study was designed to explore the mechanism underlying the effects of the main ingredient Emodin on chemosensitivity of H69AR cells to Dox. Methods: First, the growth inhibition rate of lung cancer cells and normal bronchial epithelial cells (BECs) was determined by MTT. Then, the resistance-induced epithelial-mesenchymal transition (EMT) of H69AR cells was examined by western blot and the effect of Emodin on Twist, Snail or Slug was assayed by Real-time PCR and Western blot. The activation of NF-kappa B was assayed by Western blot. Proliferation, apoptosis, migration and invasion of H69AR cells induced by Twist, Snail and Slug were also assayed by flow cytometry and transwell chamber. Results: The results showed that after administration of Dox (10?μM) with different concentrations of Emodin, the cells exhibited a dose-dependent inhibition action to H69AR cells at 48 hours. H69AR induced the expression of Twist, Snail, and Slug when compared with Dox-sensitive H69 cells. The expression of Twist, Snail, and Slug can be effectively inhibited by combination of Dox and Emodin. The reversal of resistance was associated with the inhibition of NF-kappa B. Twist, Snail and Slug promoted proliferation, migration and invasion and inhibited apoptosis. Conclusion: Our data suggest that Emodin can effectively reverse the resistance of H69AR to Dox, an effect paralleled by inhibition of EMT, cell proliferation, apoptosis, migration and invasion.
机译:> 背景: 化学抗性已成为世界范围内重要的癌症治疗问题。了解耐药机制是解决该问题并提高患者生存率的关键。阿霉素及其类似物被广泛用作抗肿瘤药物,但近年来已发现许多对阿霉素耐药的病例。阿霉素(Dox)耐药性是肺癌治疗中非常严重的现象。正如我们先前可以证明的那样,疏风解毒胶囊(SFJDC)可以有效逆转H69AR细胞对Dox的抗性,因此,本研究旨在探讨主要成分大黄素对H69AR细胞对Dox的化学敏感性的作用机理。 方法: 首先,通过MTT测定肺癌细胞和正常支气管上皮细胞(BEC)的生长抑制率。然后,通过Western印迹检查抗性诱导的H69AR细胞的上皮-间质转化(EMT),并通过实时PCR和Western印迹分析大黄素对Twist,Snail或Slug的作用。 NF-κB的活化通过蛋白质印迹法测定。还通过流式细胞仪和transwell室检测了Twist,Snail和Slug诱导的H69AR细胞的增殖,凋亡,迁移和侵袭。 结果: 结果表明,在Dox(10?μM)中加入不同浓度的大黄素后,细胞在48小时内对H69AR细胞表现出剂量依赖性的抑制作用。与对Dox敏感的H69细胞相比,H69AR诱导了Twist,Snail和Slug的表达。 Dox和Emodin的结合可有效抑制Twist,Snail和Slug的表达。抗性的逆转与NF-κB的抑制有关。扭曲,蜗牛和Slug促进增殖,迁移和侵袭并抑制细胞凋亡。 结论: 我们的数据表明大黄素可以有效逆转H69AR对Dox的耐药性,这一作用与抑制EMT,细胞增殖,凋亡,迁移和侵袭平行。

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