米内利德：一种新型治疗药物，可促进体内非小细胞肺癌细胞凋亡。
Minnelide: a novel therapeutic that promotes apoptosis in non-small cell lung carcinoma in vivo.
机构信息
Division of Basic and Translational Research, Department of Surgery, University of Minnesota, Minneapolis, Minnesota, United States of America.
出版信息
PLoS One. 2013 Oct 15;8(10):e77411. doi: 10.1371/journal.pone.0077411. eCollection 2013.
BACKGROUND
Minnelide, a pro-drug of triptolide, has recently emerged as a potent anticancer agent. The precise mechanisms of its cytotoxic effects remain unclear.
METHODS
Cell viability was studied using CCK8 assay. Cell proliferation was measured real-time on cultured cells using Electric Cell Substrate Impedence Sensing (ECIS). Apoptosis was assayed by Caspase activity on cultured lung cancer cells and TUNEL staining on tissue sections. Expression of pro-survival and anti-apoptotic genes (HSP70, BIRC5, BIRC4, BIRC2, UACA, APAF-1) was estimated by qRTPCR. Effect of Minnelide on proliferative cells in the tissue was estimated by Ki-67 staining of animal tissue sections.
RESULTS
In this study, we investigated in vitro and in vivo antitumor effects of triptolide/Minnelide in non-small cell lung carcinoma (NSCLC). Triptolide/Minnelide exhibited anti-proliferative effects and induced apoptosis in NSCLC cell lines and NSCLC mouse models. Triptolide/Minnelide significantly down-regulated the expression of pro-survival and anti-apoptotic genes (HSP70, BIRC5, BIRC4, BIRC2, UACA) and up-regulated pro-apoptotic APAF-1 gene, in part, via attenuating the NF-κB signaling activity.
CONCLUSION
In conclusion, our results provide supporting mechanistic evidence for Minnelide as a potential in NSCLC.
背景
米内利德是雷公藤红素的前体药物，最近已成为一种有效的抗癌药物。其细胞毒性作用的确切机制尚不清楚。
方法
使用 CCK8 法研究细胞活力。使用电动细胞基质阻抗感应（ECIS）在培养的细胞上实时测量细胞增殖。通过 Caspase 活性测定和组织切片 TUNEL 染色检测培养的肺癌细胞凋亡。通过 qRT-PCR 估计抗凋亡和抗凋亡基因（HSP70、BIRC5、BIRC4、BIRC2、UACA、APAF-1）的表达。通过 Ki-67 染色评估米内利德对动物组织切片中增殖细胞的影响。
结果
在这项研究中，我们研究了雷公藤红素/米内利德在非小细胞肺癌（NSCLC）中的体外和体内抗肿瘤作用。雷公藤红素/米内利德在 NSCLC 细胞系和 NSCLC 小鼠模型中表现出抗增殖作用，并诱导细胞凋亡。雷公藤红素/米内利德显著下调了抗凋亡基因（HSP70、BIRC5、BIRC4、BIRC2、UACA）的表达，并上调了促凋亡基因 APAF-1 的表达，部分通过抑制 NF-κB 信号活性。
结论
总之，我们的结果为米内利德作为 NSCLC 的潜在治疗药物提供了支持性的机制证据。
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