Resveratrol Combined with 17β-Estradiol Prevents IL-1β Induced Apoptosis in Human Nucleus Pulposus Via The PI3K/AKT/Mtor and PI3K/AKT/GSK-3β Pathway

Backgrounds: Nucleus pulposus (NP) apoptosis is mainly charged for the pathological process of Intervertebral disc degeneration (IVDD). Our previous study revealed that Resveratrol (RSV) combined with 17 beta-estradiol (E2) was more effective in cutting down IL-1 beta induced NP cell apoptosis via PI3K/AKT pathway. The present study further evaluated the effect of RSV and E2 in the anti-apoptosis process of IVDD. Methods: Human nucleus pulposus (NP) cells culture system and IL-1 beta inducing apoptosis model were constructed in this research. RSV and E2 were used to inhibit apoptosis. FACS (Fluorescence-activated cell sorting) and CCK-8 (Cell Counting Kit-8) assays were respectively used to determine apoptotic incidence and cell viability of NP cells. Quantitative RT-PCR was used to determine expression of target genes in mRNA level, and western blot analysis was performed to detect the changes of related protein expression. Results: RSV combined with E2 attenuated IL-1 beta-induced cell apoptosis and recovered cell viability. Blockers for mTOR and GSK-3 beta abated the effect of RSV and E2. RSV combined with E2 obviously increased activated P-mTOR and P-GSK-3 beta, which contributes to the downregulation of caspase-3. Activated P-NF-kappa B was not involved in the anti-apoptosis process of RSV and E2. Conclusion: Combination of Resveratrol and 17 beta-estradiol efficiently resisted IL-1 beta induced apoptosis of NP cell, mainly through PI3K/AKT/mTOR/caspase-3 and PI3K/AKT/GSK-3 beta pathway.