Effective Delivery of siRNA-Loaded Nanoparticles for Overcoming Oxaliplatin Resistance in Colorectal Cancer
Chemotherapy resistance represents a formidable obstacle in advanced or metastatic colorectal cancer (CRC) patients. It is reported that ATPase copper transporting alpha (ATP7A) plays an important role in chemotherapy resistance in CRC. Here, we identified ATP7A as a potentially key gene of OXA resi...
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Format: | Article |
Language: | English |
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Frontiers Media S.A.
2022-02-01
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Series: | Frontiers in Oncology |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.827891/full |
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author | Yue Zhou Yue Zhou Yue Zhou Qing Zhang Qing Zhang Qing Zhang Qing Zhang Minjia Wang Minjia Wang Minjia Wang Minjia Wang Chengzhi Huang Chengzhi Huang Chengzhi Huang Xueqing Yao Xueqing Yao Xueqing Yao Xueqing Yao |
author_facet | Yue Zhou Yue Zhou Yue Zhou Qing Zhang Qing Zhang Qing Zhang Qing Zhang Minjia Wang Minjia Wang Minjia Wang Minjia Wang Chengzhi Huang Chengzhi Huang Chengzhi Huang Xueqing Yao Xueqing Yao Xueqing Yao Xueqing Yao |
author_sort | Yue Zhou |
collection | DOAJ |
description | Chemotherapy resistance represents a formidable obstacle in advanced or metastatic colorectal cancer (CRC) patients. It is reported that ATPase copper transporting alpha (ATP7A) plays an important role in chemotherapy resistance in CRC. Here, we identified ATP7A as a potentially key gene of OXA resistance in CRC. The patients with higher expression of ATP7A tended to have platinum drug resistance. While the lower expression of ATP7A by siRNA knockdown resulted in enhancement of OXA sensitivity and increased OXA-induced apoptosis. Further, we demonstrated a novel and safe strategy to increase CRC chemosensitivity by delivering siRNA into tumor cells via a novel nanoparticle, DAN. In summary, our study provided a novel nanocarrier-based delivery of ATP7A to interfere in a key gene of chemo-resistance in CRC, which may be a novel therapeutic strategy to overcome chemotherapy resistance in CRC. |
first_indexed | 2024-04-13T16:35:30Z |
format | Article |
id | doaj.art-c52e4a1c507e46468a91a490baa16035 |
institution | Directory Open Access Journal |
issn | 2234-943X |
language | English |
last_indexed | 2024-04-13T16:35:30Z |
publishDate | 2022-02-01 |
publisher | Frontiers Media S.A. |
record_format | Article |
series | Frontiers in Oncology |
spelling | doaj.art-c52e4a1c507e46468a91a490baa160352022-12-22T02:39:26ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-02-011210.3389/fonc.2022.827891827891Effective Delivery of siRNA-Loaded Nanoparticles for Overcoming Oxaliplatin Resistance in Colorectal CancerYue Zhou0Yue Zhou1Yue Zhou2Qing Zhang3Qing Zhang4Qing Zhang5Qing Zhang6Minjia Wang7Minjia Wang8Minjia Wang9Minjia Wang10Chengzhi Huang11Chengzhi Huang12Chengzhi Huang13Xueqing Yao14Xueqing Yao15Xueqing Yao16Xueqing Yao17The Second School of Clinical Medicine, Southern Medical University, Guangzhou, ChinaDepartment of Gastrointestinal Surgery, Ganzhou Municipal Hospital, Ganzhou, ChinaDepartment of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaThe Second School of Clinical Medicine, Southern Medical University, Guangzhou, ChinaDepartment of Gastrointestinal Surgery, Ganzhou Municipal Hospital, Ganzhou, ChinaDepartment of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaDepartment of Gastrointestinal and Anorectal Surgery, The First People’s Hospital of Zhaoqing, Zhaoqing, ChinaThe Second School of Clinical Medicine, Southern Medical University, Guangzhou, ChinaDepartment of Gastrointestinal Surgery, Ganzhou Municipal Hospital, Ganzhou, ChinaDepartment of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaSchool of Medicine, South China University of Technology, Guangzhou, ChinaDepartment of Gastrointestinal Surgery, Ganzhou Municipal Hospital, Ganzhou, ChinaDepartment of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaSchool of Medicine, South China University of Technology, Guangzhou, ChinaThe Second School of Clinical Medicine, Southern Medical University, Guangzhou, ChinaDepartment of Gastrointestinal Surgery, Ganzhou Municipal Hospital, Ganzhou, ChinaDepartment of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaSchool of Medicine, South China University of Technology, Guangzhou, ChinaChemotherapy resistance represents a formidable obstacle in advanced or metastatic colorectal cancer (CRC) patients. It is reported that ATPase copper transporting alpha (ATP7A) plays an important role in chemotherapy resistance in CRC. Here, we identified ATP7A as a potentially key gene of OXA resistance in CRC. The patients with higher expression of ATP7A tended to have platinum drug resistance. While the lower expression of ATP7A by siRNA knockdown resulted in enhancement of OXA sensitivity and increased OXA-induced apoptosis. Further, we demonstrated a novel and safe strategy to increase CRC chemosensitivity by delivering siRNA into tumor cells via a novel nanoparticle, DAN. In summary, our study provided a novel nanocarrier-based delivery of ATP7A to interfere in a key gene of chemo-resistance in CRC, which may be a novel therapeutic strategy to overcome chemotherapy resistance in CRC.https://www.frontiersin.org/articles/10.3389/fonc.2022.827891/fulloxaliplatinchemoresistancesiRNA deliverycolorectal cancerATP7A |
spellingShingle | Yue Zhou Yue Zhou Yue Zhou Qing Zhang Qing Zhang Qing Zhang Qing Zhang Minjia Wang Minjia Wang Minjia Wang Minjia Wang Chengzhi Huang Chengzhi Huang Chengzhi Huang Xueqing Yao Xueqing Yao Xueqing Yao Xueqing Yao Effective Delivery of siRNA-Loaded Nanoparticles for Overcoming Oxaliplatin Resistance in Colorectal Cancer Frontiers in Oncology oxaliplatin chemoresistance siRNA delivery colorectal cancer ATP7A |
title | Effective Delivery of siRNA-Loaded Nanoparticles for Overcoming Oxaliplatin Resistance in Colorectal Cancer |
title_full | Effective Delivery of siRNA-Loaded Nanoparticles for Overcoming Oxaliplatin Resistance in Colorectal Cancer |
title_fullStr | Effective Delivery of siRNA-Loaded Nanoparticles for Overcoming Oxaliplatin Resistance in Colorectal Cancer |
title_full_unstemmed | Effective Delivery of siRNA-Loaded Nanoparticles for Overcoming Oxaliplatin Resistance in Colorectal Cancer |
title_short | Effective Delivery of siRNA-Loaded Nanoparticles for Overcoming Oxaliplatin Resistance in Colorectal Cancer |
title_sort | effective delivery of sirna loaded nanoparticles for overcoming oxaliplatin resistance in colorectal cancer |
topic | oxaliplatin chemoresistance siRNA delivery colorectal cancer ATP7A |
url | https://www.frontiersin.org/articles/10.3389/fonc.2022.827891/full |
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