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The sesquiterpene lactone eupatolide induces apoptosis in non-small cell lung cancer cells by suppressing STAT3 signaling
Environmental Toxicology and Pharmacology ( IF 4.3 ) Pub Date : 2020-10-20 , DOI: 10.1016/j.etap.2020.103513
Xiaoxu Ma , Kai Wu , Aiguo Xu , Pengfei Jiao , Huiling Li , Lihua Xing

We aimed to evaluate the role of a natural sesquiterpene lactone, eupatolide, in non-small-cell lung cancer (NSCLC) and further explore its underlying mechanism on regulating the activation of signal transducer and activator of transcription 3 (STAT3), which is thought to have carcinogenic function in a variety of malignancies including lung cancer. Cell survival was measured by Cell Counting Kit-8 assay. in vivo experiments were performed by inoculating NSCLC cells into nude mice. Western blot and qRT-PCR were applied to detect the activation level of STAT3 and the mRNA levels of anti-apoptotic markers. The cell apoptosis was measured by Annexin V-FITC/PI Apoptosis Detection Kit. Our results showed that eupatolide suppressed the survival of NSCLC cells in a dose and time dependent manner. Furthermore, eupatolide increased the anti-tumor activity of the chemotherapeutic drugs cisplatin and 5-Fluoracil (5-FU). The xenograft study revealed that eupatolide suppressed tumor growth of NSCLC cells in vivo. Furthermore, eupatolide induced apoptosis by suppressing the activation of STAT3 in NSCLC cells. Sustained activation or knockdown of STAT3 suppressed and enhanced the activity of eupatolide, respectively. This paper is the first to report that eupatolide could effectively inhibit NSCLC progression, suggesting that eupatolide might be utilized as a novel STAT3 inhibitor for treating NSCLC.



中文翻译:

倍半萜内酯紫杉醇内酯通过抑制STAT3信号转导诱导非小细胞肺癌细胞凋亡

我们旨在评估天然倍半萜内酯-紫杉醇在非小细胞肺癌(NSCLC)中的作用,并进一步探讨其调控信号转导子和转录激活子3(STAT3)激活的潜在机制。在包括肺癌在内的多种恶性肿瘤中具有致癌作用。细胞存活通过Cell Counting Kit-8测定法测量。体内通过将NSCLC细胞接种到裸鼠中进行实验。采用Western blot和qRT-PCR检测STAT3的激活水平和抗凋亡标记物的mRNA水平。通过Annexin V-FITC / PI凋亡检测试剂盒测量细胞凋亡。我们的结果表明,依托泊利特以剂量和时间依赖性方式抑制NSCLC细胞的存活。此外,依托泊利特提高了化疗药物顺铂和5-氟尿嘧啶(5-FU)的抗肿瘤活性。异种移植研究表明,依托泊利特在体内可抑制NSCLC细胞的肿瘤生长。此外,依托泊利特通过抑制NSCLC细胞中STAT3的激活来诱导凋亡。STAT3的持续激活或敲低分别抑制和增强了eupatolide的活性。这篇论文是第一个报道依托泊利特可以有效抑制NSCLC进展的报道,这表明依托泊利特可能被用作治疗STAT3的新型STAT3抑制剂。

更新日期:2020-11-13
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