Lenalidomide improves H(2)O(2)-induced PC12 cell injury by blocking the Notch signaling pathway

Lenalidomide (LEN) has been reported to exert antitumor, anti-inflammatory, anti-angiogenic and immunomodulatory activities. However, the effects of LEN in spinal cord injury (SCI) are yet to be fully elucidated. The present study was conducted to identify whether LEN has a healing effect on SCI and to determine the underlying mechanism of action. The viability of H(2)O(2)-stimulated PC12 cells was detected using a Cell Counting Kit-8 assay. The viability of PC12 cells treated with LEN was examined with an MTT assay. The level of lactate dehydrogenase (LDH) was measured using an LDH assay kit, while the levels of the oxidative stress-related factors malondialdehyde, superoxide dismutase, glutathione peroxidase and catalase in PC12 cells were determined using commercial kits. Oxidative stress-related proteins were examined via western blotting. PC12 cell apoptosis was observed using a TUNEL assay, while apoptosis markers and Notch signaling-related proteins were examined via western blotting. The results of the present study demonstrated that H(2)O(2) decreased PC12 cell viability in a dose-dependent manner. However, treatment with LEN significantly improved the viability of H(2)O(2)-stimulated PC12 cells and alleviated H(2)O(2)-induced cytotoxic injury. Additionally, LEN treatment inhibited the oxidative stress and apoptosis induced by H(2)O(2) in PC12 cells. Notch signaling-related protein expression was downregulated after LEN treatment in H(2)O(2)-stimulated PC12 cells. In addition, a Notch agonist reversed the effects of LEN on H(2)O(2)-induced oxidative stress and PC12 cell apoptosis. In summary, it was demonstrated that LEN alleviated the H(2)O(2)-induced injury of PC12 cells by blocking the Notch signaling pathway, suggesting the value of applying LEN to the treatment of SCI.