PD-1-siRNA Delivered by Attenuated Salmonella Enhances the Antitumor Effect of Chloroquine in Colon Cancer

The widespread appearance of drug tolerance and the low efficiency of single treatment have severely affected the survival time of the patients with colorectal cancer. Exploring new treatment options and combined treatment strategies have become the key to improving the prognosis. The combination of...

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Main Authors: Shuya Lu, Jianhui Gao, Huijie Jia, Yang Li, Yongbin Duan, Fuyang Song, Zhiang Liu, Shuai Ma, Mingyong Wang, Tiesuo Zhao, Jiateng Zhong
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-07-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2021.707991/full
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author Shuya Lu
Shuya Lu
Jianhui Gao
Jianhui Gao
Jianhui Gao
Huijie Jia
Huijie Jia
Yang Li
Yang Li
Yongbin Duan
Yongbin Duan
Fuyang Song
Fuyang Song
Zhiang Liu
Zhiang Liu
Shuai Ma
Shuai Ma
Mingyong Wang
Tiesuo Zhao
Tiesuo Zhao
Jiateng Zhong
Jiateng Zhong
Jiateng Zhong
Jiateng Zhong
Jiateng Zhong
author_facet Shuya Lu
Shuya Lu
Jianhui Gao
Jianhui Gao
Jianhui Gao
Huijie Jia
Huijie Jia
Yang Li
Yang Li
Yongbin Duan
Yongbin Duan
Fuyang Song
Fuyang Song
Zhiang Liu
Zhiang Liu
Shuai Ma
Shuai Ma
Mingyong Wang
Tiesuo Zhao
Tiesuo Zhao
Jiateng Zhong
Jiateng Zhong
Jiateng Zhong
Jiateng Zhong
Jiateng Zhong
author_sort Shuya Lu
collection DOAJ
description The widespread appearance of drug tolerance and the low efficiency of single treatment have severely affected the survival time of the patients with colorectal cancer. Exploring new treatment options and combined treatment strategies have become the key to improving the prognosis. The combination of immunotherapy and chemotherapy have shown good clinical expectations. Here, we studied the cooperative effects of chloroquine, an anti-malarial drug that is now widely used in anti-tumor research, and RNA interference (RNAi) targeting the immune checkpoint molecule Programmed Death-1 (PD-1) delivered with attenuated Salmonella. Our results show that chloroquine can not only significantly inhibit the survival of colon cancer cells and induce apoptosis, but also effectively inhibit cell invasion and migration. The results of in vivo experiments show that chloroquine can increase the expression of PD-1 in tumor tissues. Combining chloroquine and PD-1 siRNA can further inhibit the growth and metastases of colon cancer and induce apoptosis. The mechanism underlying this phenomenon is the occurrence of chloroquine-induced apoptosis and the effective immune response caused by the attenuated Salmonella carrying PD-1 siRNA. This study suggests that the combined application of PD-1-based immunotherapy and anti-cancer drugs has become a new expectation for clinical treatment of colorectal cancer.
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spelling doaj.art-63e8eac6ef6b43fe985a90136dc81f322022-12-21T17:43:16ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-07-011210.3389/fimmu.2021.707991707991PD-1-siRNA Delivered by Attenuated Salmonella Enhances the Antitumor Effect of Chloroquine in Colon CancerShuya Lu0Shuya Lu1Jianhui Gao2Jianhui Gao3Jianhui Gao4Huijie Jia5Huijie Jia6Yang Li7Yang Li8Yongbin Duan9Yongbin Duan10Fuyang Song11Fuyang Song12Zhiang Liu13Zhiang Liu14Shuai Ma15Shuai Ma16Mingyong Wang17Tiesuo Zhao18Tiesuo Zhao19Jiateng Zhong20Jiateng Zhong21Jiateng Zhong22Jiateng Zhong23Jiateng Zhong24Department of Pathology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, ChinaDepartment of Pathology, Xinxiang Medical University, Xinxiang, ChinaDepartment of Pathology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, ChinaDepartment of Pathology, Xinxiang Medical University, Xinxiang, ChinaCollege of Forensic Medicine, Xi’an Jiaotong University Health Science Center, Xi’an, ChinaDepartment of Pathology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, ChinaDepartment of Pathology, Xinxiang Medical University, Xinxiang, ChinaInstitute of Precision Medicine, Xinxiang Medical University, Xinxiang, ChinaXinxiang Key Laboratory of Tumor Vaccine and Immunotherapy, Xinxiang Medical University, Xinxiang, ChinaDepartment of Pathology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, ChinaDepartment of Pathology, Xinxiang Medical University, Xinxiang, ChinaDepartment of Pathology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, ChinaDepartment of Pathology, Xinxiang Medical University, Xinxiang, ChinaInstitute of Precision Medicine, Xinxiang Medical University, Xinxiang, ChinaXinxiang Key Laboratory of Tumor Vaccine and Immunotherapy, Xinxiang Medical University, Xinxiang, ChinaDepartment of Pathology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, ChinaDepartment of Pathology, Xinxiang Medical University, Xinxiang, ChinaLaboratory Medicine, Xinxiang Medical University, Xinxiang, ChinaInstitute of Precision Medicine, Xinxiang Medical University, Xinxiang, ChinaXinxiang Key Laboratory of Tumor Vaccine and Immunotherapy, Xinxiang Medical University, Xinxiang, ChinaDepartment of Pathology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, ChinaDepartment of Pathology, Xinxiang Medical University, Xinxiang, ChinaInstitute of Precision Medicine, Xinxiang Medical University, Xinxiang, ChinaXinxiang Key Laboratory of Tumor Vaccine and Immunotherapy, Xinxiang Medical University, Xinxiang, ChinaLaboratory of Molecular Biology of Tumor Reversal, Xinxiang Medical University, Xinxiang, ChinaThe widespread appearance of drug tolerance and the low efficiency of single treatment have severely affected the survival time of the patients with colorectal cancer. Exploring new treatment options and combined treatment strategies have become the key to improving the prognosis. The combination of immunotherapy and chemotherapy have shown good clinical expectations. Here, we studied the cooperative effects of chloroquine, an anti-malarial drug that is now widely used in anti-tumor research, and RNA interference (RNAi) targeting the immune checkpoint molecule Programmed Death-1 (PD-1) delivered with attenuated Salmonella. Our results show that chloroquine can not only significantly inhibit the survival of colon cancer cells and induce apoptosis, but also effectively inhibit cell invasion and migration. The results of in vivo experiments show that chloroquine can increase the expression of PD-1 in tumor tissues. Combining chloroquine and PD-1 siRNA can further inhibit the growth and metastases of colon cancer and induce apoptosis. The mechanism underlying this phenomenon is the occurrence of chloroquine-induced apoptosis and the effective immune response caused by the attenuated Salmonella carrying PD-1 siRNA. This study suggests that the combined application of PD-1-based immunotherapy and anti-cancer drugs has become a new expectation for clinical treatment of colorectal cancer.https://www.frontiersin.org/articles/10.3389/fimmu.2021.707991/fullcolon cancerSalmonellachloroquinePD-1siRNA
spellingShingle Shuya Lu
Shuya Lu
Jianhui Gao
Jianhui Gao
Jianhui Gao
Huijie Jia
Huijie Jia
Yang Li
Yang Li
Yongbin Duan
Yongbin Duan
Fuyang Song
Fuyang Song
Zhiang Liu
Zhiang Liu
Shuai Ma
Shuai Ma
Mingyong Wang
Tiesuo Zhao
Tiesuo Zhao
Jiateng Zhong
Jiateng Zhong
Jiateng Zhong
Jiateng Zhong
Jiateng Zhong
PD-1-siRNA Delivered by Attenuated Salmonella Enhances the Antitumor Effect of Chloroquine in Colon Cancer
Frontiers in Immunology
colon cancer
Salmonella
chloroquine
PD-1
siRNA
title PD-1-siRNA Delivered by Attenuated Salmonella Enhances the Antitumor Effect of Chloroquine in Colon Cancer
title_full PD-1-siRNA Delivered by Attenuated Salmonella Enhances the Antitumor Effect of Chloroquine in Colon Cancer
title_fullStr PD-1-siRNA Delivered by Attenuated Salmonella Enhances the Antitumor Effect of Chloroquine in Colon Cancer
title_full_unstemmed PD-1-siRNA Delivered by Attenuated Salmonella Enhances the Antitumor Effect of Chloroquine in Colon Cancer
title_short PD-1-siRNA Delivered by Attenuated Salmonella Enhances the Antitumor Effect of Chloroquine in Colon Cancer
title_sort pd 1 sirna delivered by attenuated salmonella enhances the antitumor effect of chloroquine in colon cancer
topic colon cancer
Salmonella
chloroquine
PD-1
siRNA
url https://www.frontiersin.org/articles/10.3389/fimmu.2021.707991/full
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