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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Main Authors: Yue Zhou, Qing Zhang, Minjia Wang, Chengzhi Huang, Xueqing Yao
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-02-01
Series:Frontiers in Oncology
Subjects:
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.
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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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