Mechanisms of PDGF siRNA-mediated inhibition of bone cancer pain in the spinal cord

Yang Xu; Jia Liu; Mu He; Ran Liu; Visar Belegu; Ping Dai; Wei Liu; Wei Wang; Qing Jie Xia; Fei Fei Shang; Chao Zhi Luo; Xue Zhou; Su Liu; Johnw McDonald; Jin Liu; Yun Xia Zuo; Fei Liu; Ting Hua Wang

doi:10.1038/srep27512

Mechanisms of PDGF siRNA-mediated inhibition of bone cancer pain in the spinal cord

Yang Xu, Jia Liu, Mu He, Ran Liu, Visar Belegu, Ping Dai, Wei Liu, Wei Wang, Qing Jie Xia, Fei Fei Shang, Chao Zhi Luo, Xue Zhou, Su Liu, Johnw McDonald, Jin Liu, Yun Xia Zuo, Fei Liu, Ting Hua Wang

School of Medicine

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

Abstract

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.

Original language	English (US)
Article number	27512
Journal	Scientific reports
Volume	6
DOIs	https://doi.org/10.1038/srep27512
State	Published - Jun 10 2016

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@article{ee249b27312242458afe07c8eeda5c8d,

title = "Mechanisms of PDGF siRNA-mediated inhibition of bone cancer pain in the spinal cord",

abstract = "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.",

author = "Yang Xu and Jia Liu and Mu He and Ran Liu and Visar Belegu and Ping Dai and Wei Liu and Wei Wang and Xia, {Qing Jie} and Shang, {Fei Fei} and Luo, {Chao Zhi} and Xue Zhou and Su Liu and Johnw McDonald and Jin Liu and Zuo, {Yun Xia} and Fei Liu and Wang, {Ting Hua}",

note = "Funding Information: This work was supported by grants from the National Natural Science Foundation of China (Grant No. 81271358 and No. 81171176). It also supported by Specialized Research Fund for the Doctoral Program of Higher Education (SRFDP) of China (Grant No. 20130181110077).",

year = "2016",

month = jun,

day = "10",

doi = "10.1038/srep27512",

language = "English (US)",

volume = "6",

journal = "Scientific reports",

issn = "2045-2322",

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TY - JOUR

T1 - Mechanisms of PDGF siRNA-mediated inhibition of bone cancer pain in the spinal cord

AU - Xu, Yang

AU - Liu, Jia

AU - He, Mu

AU - Liu, Ran

AU - Belegu, Visar

AU - Dai, Ping

AU - Liu, Wei

AU - Wang, Wei

AU - Xia, Qing Jie

AU - Shang, Fei Fei

AU - Luo, Chao Zhi

AU - Zhou, Xue

AU - Liu, Su

AU - McDonald, Johnw

AU - Liu, Jin

AU - Zuo, Yun Xia

AU - Liu, Fei

AU - Wang, Ting Hua

N1 - Funding Information: This work was supported by grants from the National Natural Science Foundation of China (Grant No. 81271358 and No. 81171176). It also supported by Specialized Research Fund for the Doctoral Program of Higher Education (SRFDP) of China (Grant No. 20130181110077).

PY - 2016/6/10

Y1 - 2016/6/10

N2 - 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.

AB - 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.

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ER -

Mechanisms of PDGF siRNA-mediated inhibition of bone cancer pain in the spinal cord

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