Open AccessMechanisms of PDGF siRNA-mediated inhibition of bone cancer pain in the spinal cord
Author(s) -
Yang Xu,
Jia Liu,
Min He,
Ran Liu,
Visar Belegu,
Pengcheng Dai,
Wei Liu,
Wei Wang,
Qing Xia,
Fei Shang,
Chao Zhi Luo,
Xue Zhou,
Su Liu,
Johnw McDonald,
Jin Liu,
Yun Xia Zuo,
Fei Liu,
TingHua Wang
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep27512
Subject(s) - bone cancer , medicine , platelet derived growth factor receptor , protein kinase b , cancer research , mapk/erk pathway , cancer , small interfering rna , pi3k/akt/mtor pathway , spinal cord , pharmacology , growth factor , signal transduction , biology , transfection , cell culture , microbiology and biotechnology , receptor , psychiatry , genetics
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.