title: Downregulation of PI3Kcb utilizing adenovirus-mediated transfer of siRNA attenuates bone cancer pain.
abstract: Phosphatidylinositol 3-kinase (PI3K) signaling plays a pivotal role in intracellular signal transduction pathways involved in chronic pain states. PI3K is implicated in pathomechanisms of enhanced synaptic strength, such as wind-up and central sensitization in the spinal dorsal horn. The PI3Kcb gene encoding the class 1A PI3K catalytic subunit p110beta is one of the most important molecular of the P13K signaling pathway. Here, we used small interfering RNA (siRNA) targeted to PI3Kcb by adenovirus-mediated transfer, to determine whether inhibition of PI3Kcb was a potential therapeutic target for bone cancer pain (BCP). In this study, treatment of BCP model in rats with PI3Kcb-specific siRNA resulted in inhibited pain-related behavior. Depletion of PI3Kcb decreased the protein levels of spinal PI3Kcb and phospho-Akt (P-Akt)-downstream targets of PI3K. Knockdown of PI3Kcb by siRNA also induced decreased expression of GFAP and OX42, suggesting that the upregulation of spinal PI3Kcb may increase glia excitability, at least in part by regulating glia message. Our findings suggest that siRNA-mediated gene silencing of PI3Kcb may be a useful therapeutic strategy for BCP.
authors.affiliation: Department of Gastroenterology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology Wuhan 430022, Hubei, PR China.
authors.forename: Huan-Jun
authors.initials: HJ
authors.lastname: Huang
authors.affiliation: Department of Neurology, Wuhan Central Hospital Wuhan 430014, Hubei, PR China.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000256:Adenoviridae; D000818:Animals; D001859:Bone Neoplasms / Q000150:complications* / Q000235:genetics; D045744:Cell Line, Tumor; D058541:Class II Phosphatidylinositol 3-Kinases / Q000235:genetics*; D015536:Down-Regulation; D005260:Female; D020868:Gene Silencing; D018014:Gene Transfer Techniques; D009368:Neoplasm Transplantation; D010146:Pain / Q000209:etiology* / Q000235:genetics; D059408:Pain Management; D010147:Pain Measurement; D017288:Pain Threshold; D034741:RNA, Small Interfering; D051381:Rats
chemical_list: D034741:RNA, Small Interfering; D058541:Class II Phosphatidylinositol 3-Kinases; C502616:PIK3C2B protein, human
keywords: Bone cancer pain; adenovirus vector; phosphatidylinositol 3-kinase; phospho-Akt; small interfering RNA