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葫芦素A对A-549肺癌细胞的抗肿瘤和凋亡作用是通过G2/M期细胞周期阻滞和m-TOR/PI3K/AKT信号通路介导的。

ANTITUMOR AND APOPTOTIC EFFECTS OF CUCURBITACIN A IN A-549 LUNG CARCINOMA CELLS IS MEDIATED VIA G2/M CELL CYCLE ARREST AND M-TOR/PI3K/AKT SIGNALLING PATHWAY.

作者信息

Wang Wen-Dong, Liu Yan, Su Yuan, Xiong Xian-Zhi, Shang Dan, Xu Juan-Juan, Liu Hong-Ju

机构信息

Department of Thoracic surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Department of Respiratory Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

出版信息

Afr J Tradit Complement Altern Med. 2017 Jan 13;14(2):75-82. doi: 10.21010/ajtcam.v14i2.9. eCollection 2017.

Abstract

BACKGROUND

The main aim of this study was to demonstrate the antitumor potential of cucurbitacin A on A-549 NSCLC (non-small cell lung cancer cells). The effects of Cucurbitacin A on apoptotic induction, cell physic, cell cycle failure and m-TOR/PI3K/Akt signalling pathway were also investigated in the present study.

MATERIALS AND METHODS

MTT assay and clonogenic assay were carried out to study effects of this compound on cell cytotoxicity and colony forming tendency in A-549 cells. Moreover, phase and fluorescence microscopic techniques were used to examine the effects on cell morphology and induction of apoptosis. The effects on cell cycle phase distribution were investigated by flow cytometry and effects on m-TOR/PI3K/Akt signalling proteins were assessed by western blot analysis.

RESULTS

Results showed that cucurbitacin A induced dose-dependent cytotoxic effects along with suppressing the colony forming tendency in these cells. Cucurbitacin A also induced morphological changes in these cells featuring chromatin condensation, cell shrinkage and apoptotic body formation. G2/M phase cell cycle collapse was also induced by Cucurbitacin A along with inhibition of expression levels of m-TOR/PI3K/Akt proteins.

CONCLUSIONS

In conclusion, cucurbitacin A inhibits cancer growth in A-549 NSCLC cells by inducing apoptosis, targeting m-TOR/PI3K/Akt signalling pathway and G2/M cell cycle.

摘要

背景

本研究的主要目的是证明葫芦素A对A-549非小细胞肺癌(非小细胞肺癌细胞)的抗肿瘤潜力。本研究还探讨了葫芦素A对凋亡诱导、细胞物理性质、细胞周期阻滞和m-TOR/PI3K/Akt信号通路的影响。

材料与方法

采用MTT法和克隆形成试验研究该化合物对A-549细胞的细胞毒性和集落形成倾向的影响。此外,利用相差显微镜和荧光显微镜技术检测其对细胞形态和凋亡诱导的影响。通过流式细胞术研究其对细胞周期阶段分布的影响,并通过蛋白质印迹分析评估其对m-TOR/PI3K/Akt信号蛋白的影响。

结果

结果表明,葫芦素A诱导剂量依赖性细胞毒性,并抑制这些细胞的集落形成倾向。葫芦素A还诱导这些细胞发生形态学变化,表现为染色质浓缩、细胞皱缩和凋亡小体形成。葫芦素A还诱导G2/M期细胞周期阻滞,并抑制m-TOR/PI3K/Akt蛋白的表达水平。

结论

总之,葫芦素A通过诱导凋亡、靶向m-TOR/PI3K/Akt信号通路和G2/M细胞周期来抑制A-549非小细胞肺癌细胞的生长。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9f5/5446468/34af195bb6b6/AJTCAM-14-75-g001.jpg

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