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钙、P38丝裂原活化蛋白激酶在双氢青蒿素诱导肺癌PC - 14细胞凋亡中的作用

The role of calcium, P38 MAPK in dihydroartemisinin-induced apoptosis of lung cancer PC-14 cells.

作者信息

Mu Deguang, Zhang Wei, Chu Dongling, Liu Tonggang, Xie Yonghong, Fu Enqing, Jin Faguang

机构信息

Department of Respiratory Disease, Tangdu Hospital, Fourth Military Medical University, 1# Xinsi Road, Xi'an city, Shaanxi Province, 710038, China.

出版信息

Cancer Chemother Pharmacol. 2008 Apr;61(4):639-45. doi: 10.1007/s00280-007-0517-5. Epub 2007 Jul 4.

Abstract

INTRODUCTION

Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin isolated from the traditional Chinese herb Artemisia annua, is an effective novel antimalarial drug. Recent studies suggest that it also has anticancer effect.

PURPOSE

The present study was designed to investigate the effects of DHA on cultured human lung cancer cells (PC-14 cells) to better understand its apoptosis and apoptosis-related factors in vitro.

METHODS

The cell viability was measured by MTT assay. The apoptosis induction was examined by DNA ladder and flow cytometry. The intracellular-free calcium concentration in the lung cancer cells were evaluated by laser scanning confocal microscopy with Fura-3/AM as probe. The associated gene expression was examined by Western blot.

RESULTS

After treatment with DHA, a decrease in the viability of PC-14 cells and apoptosis were observed. DHA-induced apoptosis were accompanied by an increase of Ca(2+) and activation of p38. Deleted levels of Ca(2+) by BAPTA-AM 20 microM or inhibition of p38 by its selective inhibitor SB202190 then led to decreased DHA-induced apoptosis.

CONCLUSIONS

These results demonstrated that DHA can induce apoptosis of lung cancer cell line PC-14 cells and calcium and p38 play important roles in the apoptotic signalling pathways.

摘要

引言

双氢青蒿素(DHA)是从传统中药青蒿中分离出的青蒿素的半合成衍生物,是一种有效的新型抗疟药物。最近的研究表明它也具有抗癌作用。

目的

本研究旨在探讨双氢青蒿素对培养的人肺癌细胞(PC-14细胞)的影响,以便更好地了解其在体外的凋亡及凋亡相关因子。

方法

采用MTT法检测细胞活力。通过DNA梯状条带和流式细胞术检测凋亡诱导情况。以Fura-3/AM为探针,利用激光扫描共聚焦显微镜评估肺癌细胞内的游离钙浓度。通过蛋白质免疫印迹法检测相关基因表达。

结果

用双氢青蒿素处理后,观察到PC-14细胞活力下降及凋亡。双氢青蒿素诱导的凋亡伴随着Ca(2+)增加和p38激活。用20微摩尔的BAPTA-AM消除Ca(2+)水平或用其选择性抑制剂SB202190抑制p38,随后导致双氢青蒿素诱导的凋亡减少。

结论

这些结果表明,双氢青蒿素可诱导肺癌细胞系PC-14细胞凋亡,钙和p38在凋亡信号通路中起重要作用。

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