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西达本胺联合硼替佐米对胃癌的协同抗肿瘤活性

The Synergistic Antitumor Activity of Chidamide in Combination with Bortezomib on Gastric Cancer.

作者信息

Zhang Wanjun, Niu Junwei, Ma Yongcheng, Yang Xiawan, Cao Huixia, Guo Honggang, Bao Fengchang, Haw Ahmed, Chen Yuqing, Sun Kai

机构信息

Department of Hematology, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, Henan, 450003, People's Republic of China.

Clinical Pharmacology Laboratory, Henan Provincial People's Hospital; Department of Pharmacy of Central China Fuwai Hospital, Central China Fuwai Hospital of Zhengzhou University, Zhengzhou, Henan 450003, People's Republic of China.

出版信息

Onco Targets Ther. 2020 May 6;13:3823-3837. doi: 10.2147/OTT.S240721. eCollection 2020.

Abstract

PURPOSE

The aim of this study was to investigate the antitumor effect of chidamide in combination with bortezomib on gastric cancer cell lines.

MATERIALS AND METHODS

First, the sensitivity and IC values of chidamide and bortezomib in several gastric cancer cell lines (MGC-803, BGC-823, SGC-7901, and MKN45) were measured using the CCK-8 assay. Then, the relatively insensitive gastric cancer cell lines (MGC-803 and BGC-823) were treated with low concentrations of chidamide alone, bortezomib alone, or chidamide and bortezomib combination to detect the effects on cell proliferation, apoptosis, migration, and invasion. Finally, the inhibitory effect of the combined chidamide and bortezomib treatment on MGC-803 cells was verified in vivo through tumor formation experiments in nude mice.

RESULTS

Compared with low-dose chidamide or bortezomib alone, the low-dose drug combination significantly inhibited the proliferation, migration, and invasion of MGC-803 and BGC-823 cells and induced apoptosis of the cells. The effects of the low-dose chidamide and bortezomib combination reduced the growth on gastric cancer in vivo were investigated by using a subcutaneous tumor mouse model.

CONCLUSION

Our results suggest that the combination of chidamide and bortezomib can significantly reduce the proliferation, invasion, and migration of MGC-803 and BGC-823 cells, providing a framework for the clinical evaluation of combined therapies for gastric cancers.

摘要

目的

本研究旨在探讨西达本胺联合硼替佐米对胃癌细胞系的抗肿瘤作用。

材料与方法

首先,使用CCK-8法检测西达本胺和硼替佐米在几种胃癌细胞系(MGC-803、BGC-823、SGC-7901和MKN45)中的敏感性和半数抑制浓度(IC值)。然后,用低浓度的西达本胺单独处理、硼替佐米单独处理或西达本胺与硼替佐米联合处理相对不敏感的胃癌细胞系(MGC-803和BGC-823),以检测对细胞增殖、凋亡、迁移和侵袭的影响。最后,通过裸鼠成瘤实验在体内验证西达本胺与硼替佐米联合处理对MGC-803细胞的抑制作用。

结果

与低剂量西达本胺或硼替佐米单独使用相比,低剂量药物联合使用显著抑制了MGC-803和BGC-823细胞的增殖、迁移和侵袭,并诱导了细胞凋亡。通过皮下肿瘤小鼠模型研究了低剂量西达本胺和硼替佐米联合使用对体内胃癌生长的影响。

结论

我们的结果表明,西达本胺与硼替佐米联合使用可显著降低MGC-803和BGC-823细胞的增殖、侵袭和迁移,为胃癌联合治疗的临床评估提供了框架。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/118b/7213427/41a5b15cdaa2/OTT-13-3823-g0001.jpg

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