Effects of Combination of Anti-CTLA-4 and Anti-PD-1 on Gastric Cancer Cells Proliferation, Apoptosis and Metastasis

Background/Aims: Gastric cancer (GC) is one of the most common and lethal varieties of cancers. Anticancer activities of anti-CTLA-4 and anti-PD-1 antibodies have been explored in different cancers, including GC. The study aimed to explore the role of combination therapy with anti-CTLA-4 and anti-PD...

Full description

Bibliographic Details
Main Authors: Bin Wang, Lei Qin, Mei Ren, Hao Sun
Format: Article
Language:English
Published: Cell Physiol Biochem Press GmbH & Co KG 2018-08-01
Series:Cellular Physiology and Biochemistry
Subjects:
EMT
Online Access:https://www.karger.com/Article/FullText/492876
id doaj-4daef77231a942208666ac8ea7e1f17f
record_format Article
spelling doaj-4daef77231a942208666ac8ea7e1f17f2020-11-24T21:53:21ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782018-08-0149126027010.1159/000492876492876Effects of Combination of Anti-CTLA-4 and Anti-PD-1 on Gastric Cancer Cells Proliferation, Apoptosis and MetastasisBin WangLei QinMei RenHao SunBackground/Aims: Gastric cancer (GC) is one of the most common and lethal varieties of cancers. Anticancer activities of anti-CTLA-4 and anti-PD-1 antibodies have been explored in different cancers, including GC. The study aimed to explore the role of combination therapy with anti-CTLA-4 and anti-PD-1 antibodies in GC cells, and understand the possible underlying molecular mechanism. Methods: MKN-45 and MGC-803 cells were divided into four groups, namely control, CTLA-4, PD-1, and CTLA-4&PD-1. Cell viability, cell cycle, apoptosis, migration and invasion were measured by MTT, flow cytometry, and transwell assays, respectively. Expression levels of different mRNAs and proteins associated with apoptosis, epithelial mesenchymal transition (EMT), β-catenin, MAPK, and PI3K/AKT pathways were assessed by RT-qPCR and western blot analysis, respectively. The tumor formation in vivo was examined by tumor Xenograft model assay. Results: Combination with anti-CTLA-4 and anti-PD-1 antibodies significantly suppressed cell proliferation, induced apoptosis, as well as inhibited migration, invasion, and EMT in MKN-45 and MGC-803 cells. Western blotting revealed that combination with anti-CTLA-4 and anti-PD-1 antibodies declined the activation of β-catenin, MAPK and PI3K/AKT signal pathways. Moreover, combination of anti-CTLA-4 and anti-PD-1 antibodies inhibited tumor formation in vivo. Furthermore, the mRNA levels of CTLA-4 and PD-1 were significantly decreased in si-CTLA and si-PD-1 transfected cells, and combination with si-CTLA and si-PD-1 also suppressed cell proliferation, migration, invasion, EMT and induced apoptosis in MKN-45 cells. Conclusion: Combination therapy with anti-CTLA-4 and anti-PD-1 antibodies presented the promising outcomes in GC, although further investigations are warranted.https://www.karger.com/Article/FullText/492876Gastric cancerAnti-CTLA-4 antibodyAnti-PD-1 antibodyEMTβ-catenin
collection DOAJ
language English
format Article
sources DOAJ
author Bin Wang
Lei Qin
Mei Ren
Hao Sun
spellingShingle Bin Wang
Lei Qin
Mei Ren
Hao Sun
Effects of Combination of Anti-CTLA-4 and Anti-PD-1 on Gastric Cancer Cells Proliferation, Apoptosis and Metastasis
Cellular Physiology and Biochemistry
Gastric cancer
Anti-CTLA-4 antibody
Anti-PD-1 antibody
EMT
β-catenin
author_facet Bin Wang
Lei Qin
Mei Ren
Hao Sun
author_sort Bin Wang
title Effects of Combination of Anti-CTLA-4 and Anti-PD-1 on Gastric Cancer Cells Proliferation, Apoptosis and Metastasis
title_short Effects of Combination of Anti-CTLA-4 and Anti-PD-1 on Gastric Cancer Cells Proliferation, Apoptosis and Metastasis
title_full Effects of Combination of Anti-CTLA-4 and Anti-PD-1 on Gastric Cancer Cells Proliferation, Apoptosis and Metastasis
title_fullStr Effects of Combination of Anti-CTLA-4 and Anti-PD-1 on Gastric Cancer Cells Proliferation, Apoptosis and Metastasis
title_full_unstemmed Effects of Combination of Anti-CTLA-4 and Anti-PD-1 on Gastric Cancer Cells Proliferation, Apoptosis and Metastasis
title_sort effects of combination of anti-ctla-4 and anti-pd-1 on gastric cancer cells proliferation, apoptosis and metastasis
publisher Cell Physiol Biochem Press GmbH & Co KG
series Cellular Physiology and Biochemistry
issn 1015-8987
1421-9778
publishDate 2018-08-01
description Background/Aims: Gastric cancer (GC) is one of the most common and lethal varieties of cancers. Anticancer activities of anti-CTLA-4 and anti-PD-1 antibodies have been explored in different cancers, including GC. The study aimed to explore the role of combination therapy with anti-CTLA-4 and anti-PD-1 antibodies in GC cells, and understand the possible underlying molecular mechanism. Methods: MKN-45 and MGC-803 cells were divided into four groups, namely control, CTLA-4, PD-1, and CTLA-4&PD-1. Cell viability, cell cycle, apoptosis, migration and invasion were measured by MTT, flow cytometry, and transwell assays, respectively. Expression levels of different mRNAs and proteins associated with apoptosis, epithelial mesenchymal transition (EMT), β-catenin, MAPK, and PI3K/AKT pathways were assessed by RT-qPCR and western blot analysis, respectively. The tumor formation in vivo was examined by tumor Xenograft model assay. Results: Combination with anti-CTLA-4 and anti-PD-1 antibodies significantly suppressed cell proliferation, induced apoptosis, as well as inhibited migration, invasion, and EMT in MKN-45 and MGC-803 cells. Western blotting revealed that combination with anti-CTLA-4 and anti-PD-1 antibodies declined the activation of β-catenin, MAPK and PI3K/AKT signal pathways. Moreover, combination of anti-CTLA-4 and anti-PD-1 antibodies inhibited tumor formation in vivo. Furthermore, the mRNA levels of CTLA-4 and PD-1 were significantly decreased in si-CTLA and si-PD-1 transfected cells, and combination with si-CTLA and si-PD-1 also suppressed cell proliferation, migration, invasion, EMT and induced apoptosis in MKN-45 cells. Conclusion: Combination therapy with anti-CTLA-4 and anti-PD-1 antibodies presented the promising outcomes in GC, although further investigations are warranted.
topic Gastric cancer
Anti-CTLA-4 antibody
Anti-PD-1 antibody
EMT
β-catenin
url https://www.karger.com/Article/FullText/492876
work_keys_str_mv AT binwang effectsofcombinationofantictla4andantipd1ongastriccancercellsproliferationapoptosisandmetastasis
AT leiqin effectsofcombinationofantictla4andantipd1ongastriccancercellsproliferationapoptosisandmetastasis
AT meiren effectsofcombinationofantictla4andantipd1ongastriccancercellsproliferationapoptosisandmetastasis
AT haosun effectsofcombinationofantictla4andantipd1ongastriccancercellsproliferationapoptosisandmetastasis
_version_ 1725872864842743808