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防己诺林碱通过内质网应激诱导细胞凋亡发挥对结直肠癌细胞的抗癌作用。

Fangchinoline Exerts Anticancer Effects on Colorectal Cancer Cells by Evoking Cell Apoptosis via Endoplasmic Reticulum Stress.

机构信息

Medical School of Yangzhou Polytechnic College, Yangzhou, China.

Department of Surgery of Jiangsu, Provincial Corps Hospital, Yangzhou, China.

出版信息

Bull Exp Biol Med. 2023 Mar;174(5):639-646. doi: 10.1007/s10517-023-05761-x. Epub 2023 Apr 13.

DOI:10.1007/s10517-023-05761-x
PMID:37052856
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10098992/
Abstract

We studied the anti-tumor effect of fangchinoline (FAN) against human colorectal cancer cell lines CCL-244 and SW480 and analyzed the mechanism of FAN action. The cell viability and apoptosis were assessed by MTT test and Annexin V-PI staining; caspase-3 activity was measured by Western blotting. The expression of endoplasmic reticulum stress-related proteins was assessed by real-time PCR, Western blotting, and gene transfection. It was found that FAN inhibited cell growth and induced apoptosis in human colorectal cancer cell lines CCL-244 and SW480 in a dose-dependent manner. The caspase-3 inhibitor Ac-DEVD-CHO could reverse the inhibitory effect of FAN. Moreover, FAN significantly increased the expression of endoplasmic reticulum stress-related proteins p-PERK, p-eIF2α, ATF4, and CHOP in CCL-244 and SW480 cells. In addition, endoplasmic reticulum stress inhibitor 4-phenylbutyric acid or CHOP knockdown could prevent FAN-induced apoptosis. Thus, FAN induced apoptosis of human colorectal cancer through activation of endoplasmic reticulum stress.

摘要

我们研究了汉防己甲素（FAN）对人结肠癌细胞系 CCL-244 和 SW480 的抗肿瘤作用，并分析了 FAN 的作用机制。通过 MTT 试验和 Annexin V-PI 染色评估细胞活力和细胞凋亡；通过 Western blot 测定半胱天冬酶-3（caspase-3）活性。通过实时 PCR、Western blot 和基因转染评估内质网应激相关蛋白的表达。结果发现，FAN 以剂量依赖性方式抑制人结肠癌细胞系 CCL-244 和 SW480 的细胞生长并诱导细胞凋亡。caspase-3 抑制剂 Ac-DEVD-CHO 可逆转 FAN 的抑制作用。此外，FAN 显著增加 CCL-244 和 SW480 细胞中内质网应激相关蛋白 p-PERK、p-eIF2α、ATF4 和 CHOP 的表达。此外，内质网应激抑制剂 4-苯基丁酸或 CHOP 敲低可预防 FAN 诱导的细胞凋亡。因此，FAN 通过激活内质网应激诱导人结肠癌细胞凋亡。