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伊马替尼和百里醌对结直肠癌自噬和凋亡的促进作用

Promotion of Autophagy and Apoptosis in Colorectal Cancer Exposed to Imatinib and Thymoquinone.

作者信息

El-Khouly Dalia, Thabet Nadia A, Sayed-Ahmed Mohamed, Omran Mervat M

机构信息

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ahram Canadian University, 6th of October City, Giza, Egypt.

Department of Cancer Biology, Pharmacology Unit, National Cancer Institute, Cairo University, Egypt.

出版信息

J Biochem Mol Toxicol. 2025 Apr;39(4):e70238. doi: 10.1002/jbt.70238.

Abstract

Cancer cells possess high proliferative ability and usually override apoptosis and metastasize to distant lesions. Autophagy in cancer cells is a double-edged weapon where a cross-regulation postulation between apoptosis and autophagy exists. The aim of the present study was to investigate the effect of adding Thymoquinone (TQ) to Imatinib (IM) in HCT human colorectal cancer cell line model on various apoptotic and autophagy markers. The combination doses of IM and TQ were selected according to our previous study concerned with cytotoxicity and uptake/efflux genes modulation. In the current study, the combination induced autophagy in HCT cell line which in turn enhanced apoptosis. Moreover, early apoptosis was evidenced. The induction of both autophagy and apoptosis resulted in programmed cell death. The assessment of AMPK, Par-4, apoptosis markers, colony formation assays, flow cytometry and autophagy detection by acridine orange proved this rapport.

摘要

癌细胞具有高增殖能力,通常会抑制细胞凋亡并转移至远处病灶。癌细胞中的自噬是一把双刃剑,凋亡与自噬之间存在交叉调节假说。本研究的目的是在HCT人结肠癌细胞系模型中,研究在伊马替尼(IM)中添加百里醌(TQ)对各种凋亡和自噬标志物的影响。IM和TQ的联合剂量是根据我们之前关于细胞毒性以及摄取/外排基因调节的研究选定的。在当前研究中,该联合用药在HCT细胞系中诱导了自噬,进而增强了细胞凋亡。此外,还证实了早期凋亡。自噬和凋亡的诱导均导致程序性细胞死亡。对AMPK、Par-4、凋亡标志物的评估、集落形成试验、流式细胞术以及通过吖啶橙进行的自噬检测证实了这种关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2508/11947640/d73dbda281e4/JBT-39-e70238-g001.jpg

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