Relationship between IL-17 and PI3K/Akt signaling pathway in dorsal root ganglion of rats with bone cancer pain

Abstract

Objective To investigate the relationship between interleukin-17 (IL-17) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway in the dorsal root ganglion (DRG) of rats with bone cancer pain (BCP). Methods Forty-four pathogen-free adult female unmated Sprague-Dawley rats, aged 9 weeks, weighing 180-200 g, were randomly divided into 4 groups (n=11 each) using a random number table: sham operation group (group S); BCP group (group B); BCP + IL-17 antibody group (group BI); BCP + phosphate buffer solution (the solvent) group (group BP). BCP was induced by injecting Walker256 mammary gland cancer cell suspension 10 μl into the medullary cavity of the left tibia in B, BI and BP groups, while group S received intra-tibial inoculation of 10 μl Hank′s solution.At 9-11 days after BCP, PBS 20 μl/d and IL-17 antibody (1 mg/ml) 20 μl/d were injected intrathecally once a day in BP and BI groups, respectively.Before BCP (T0), at 5 days after BCP (T1), before administration on day 9 after BCP (T2) and at 30 min after administration on day 11 after BCP (T3), the mechanical pain threshold was measured.After measurement of the pain threshold on day 11 after BCP, the animals were sacrificed, and the DRGs of the lumbar segment (L4-6) were removed for determination of the expression of PI3K, phosphorylated Akt (p-Akt) and Akt by Western blot. Results Compared with group S, the mechanical pain threshold was significantly decreased at T1-3, and the expression of PI3K and p-Akt in DRGs was significantly up-regulated in B, BI and BP groups (P 0.05). There was no significant difference in the expression of Akt in DRGs among the four groups (P>0.05). Conclusion IL-17 in the DRG is involved in the maintenance of BCP probably through activating PI3K/Akt signaling pathway in rats. Key words: Bone neoplasms; Pain; Interleukin-17; 1-Phosphatidylinositol 3-kinase; Protein-serine-threonine kinases