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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Frontiers Media S.A.
2021-07-01
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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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last_indexed | 2024-12-23T14:39:24Z |
publishDate | 2021-07-01 |
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series | Frontiers in Immunology |
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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