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Mechanisms of PDGF siRNA-mediated inhibition of bone cancer pain in the spinal cord
Patients with tumors that metastasize to bone frequently suffer from debilitating pain, and effective therapies for treating bone cancer are lacking. This study employed a novel strategy in which herpes simplex virus (HSV) carrying a small interfering RNA (siRNA) targeting platelet-derived growth fa...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4901320/ https://www.ncbi.nlm.nih.gov/pubmed/27282805 http://dx.doi.org/10.1038/srep27512 |
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author | Xu, Yang Liu, Jia He, Mu Liu, Ran Belegu, Visar Dai, Ping Liu, Wei Wang, Wei Xia, Qing-Jie Shang, Fei-Fei Luo, Chao-Zhi Zhou, Xue Liu, Su McDonald, JohnW. Liu, Jin Zuo, Yun-Xia Liu, Fei Wang, Ting-Hua |
author_facet | Xu, Yang Liu, Jia He, Mu Liu, Ran Belegu, Visar Dai, Ping Liu, Wei Wang, Wei Xia, Qing-Jie Shang, Fei-Fei Luo, Chao-Zhi Zhou, Xue Liu, Su McDonald, JohnW. Liu, Jin Zuo, Yun-Xia Liu, Fei Wang, Ting-Hua |
author_sort | Xu, Yang |
collection | PubMed |
description | Patients with tumors that metastasize to bone frequently suffer from debilitating pain, and effective therapies for treating bone cancer are lacking. This study employed a novel strategy in which herpes simplex virus (HSV) carrying a small interfering RNA (siRNA) targeting platelet-derived growth factor (PDGF) was used to alleviate bone cancer pain. HSV carrying PDGF siRNA was established and intrathecally injected into the cavum subarachnoidale of animals suffering from bone cancer pain and animals in the negative group. Sensory function was assessed by measuring thermal and mechanical hyperalgesia. The mechanism by which PDGF regulates pain was also investigated by comparing the differential expression of pPDGFRα/β and phosphorylated ERK and AKT. Thermal and mechanical hyperalgesia developed in the rats with bone cancer pain, and these effects were accompanied by bone destruction in the tibia. Intrathecal injection of PDGF siRNA and morphine reversed thermal and mechanical hyperalgesia in rats with bone cancer pain. In addition, we observed attenuated astrocyte hypertrophy, down-regulated pPDGFRα/β levels, reduced levels of the neurochemical SP, a reduction in CGRP fibers and changes in pERK/ERK and pAKT/AKT ratios. These results demonstrate that PDGF siRNA can effectively treat pain induced by bone cancer by blocking the AKT-ERK signaling pathway. |
format | Online Article Text |
id | pubmed-4901320 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-49013202016-06-13 Mechanisms of PDGF siRNA-mediated inhibition of bone cancer pain in the spinal cord Xu, Yang Liu, Jia He, Mu Liu, Ran Belegu, Visar Dai, Ping Liu, Wei Wang, Wei Xia, Qing-Jie Shang, Fei-Fei Luo, Chao-Zhi Zhou, Xue Liu, Su McDonald, JohnW. Liu, Jin Zuo, Yun-Xia Liu, Fei Wang, Ting-Hua Sci Rep Article Patients with tumors that metastasize to bone frequently suffer from debilitating pain, and effective therapies for treating bone cancer are lacking. This study employed a novel strategy in which herpes simplex virus (HSV) carrying a small interfering RNA (siRNA) targeting platelet-derived growth factor (PDGF) was used to alleviate bone cancer pain. HSV carrying PDGF siRNA was established and intrathecally injected into the cavum subarachnoidale of animals suffering from bone cancer pain and animals in the negative group. Sensory function was assessed by measuring thermal and mechanical hyperalgesia. The mechanism by which PDGF regulates pain was also investigated by comparing the differential expression of pPDGFRα/β and phosphorylated ERK and AKT. Thermal and mechanical hyperalgesia developed in the rats with bone cancer pain, and these effects were accompanied by bone destruction in the tibia. Intrathecal injection of PDGF siRNA and morphine reversed thermal and mechanical hyperalgesia in rats with bone cancer pain. In addition, we observed attenuated astrocyte hypertrophy, down-regulated pPDGFRα/β levels, reduced levels of the neurochemical SP, a reduction in CGRP fibers and changes in pERK/ERK and pAKT/AKT ratios. These results demonstrate that PDGF siRNA can effectively treat pain induced by bone cancer by blocking the AKT-ERK signaling pathway. Nature Publishing Group 2016-06-10 /pmc/articles/PMC4901320/ /pubmed/27282805 http://dx.doi.org/10.1038/srep27512 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Xu, Yang Liu, Jia He, Mu Liu, Ran Belegu, Visar Dai, Ping Liu, Wei Wang, Wei Xia, Qing-Jie Shang, Fei-Fei Luo, Chao-Zhi Zhou, Xue Liu, Su McDonald, JohnW. Liu, Jin Zuo, Yun-Xia Liu, Fei Wang, Ting-Hua Mechanisms of PDGF siRNA-mediated inhibition of bone cancer pain in the spinal cord |
title | Mechanisms of PDGF siRNA-mediated inhibition of bone cancer pain in the spinal cord |
title_full | Mechanisms of PDGF siRNA-mediated inhibition of bone cancer pain in the spinal cord |
title_fullStr | Mechanisms of PDGF siRNA-mediated inhibition of bone cancer pain in the spinal cord |
title_full_unstemmed | Mechanisms of PDGF siRNA-mediated inhibition of bone cancer pain in the spinal cord |
title_short | Mechanisms of PDGF siRNA-mediated inhibition of bone cancer pain in the spinal cord |
title_sort | mechanisms of pdgf sirna-mediated inhibition of bone cancer pain in the spinal cord |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4901320/ https://www.ncbi.nlm.nih.gov/pubmed/27282805 http://dx.doi.org/10.1038/srep27512 |
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