Sphingosine-1-phosphate activates the AKT pathway to inhibit chemotherapy induced human granulosa cell apoptosis

To investigate whether sphingosine-1-phosphate (S1P), an apoptosis-inhibitor would be able to inhibit chemotherapy induced human granulosa cell apoptosis. Cultures of primary granulosa cells were isolated from women undergoing in vitro fertilization (IVF). MTT assay was used to measure the optimum concentration of CTX and S1P acts on human granulosa cells. Granulosa cells were added with pertussis toxin (PTX), the PI3K inhibitor LY294002. Western blot analysis was used to analyze the signaling pathway of proteins and cell apoptosis. We found that S1P (10 mm) statistically significantly decreased granulosa cell apoptosis after cyclophosphamide (CTX) treatment. The decreased cell apoptosis induced by S1P was abolished after treatment with LY294002, PI3K inhibitor. CONCLUSIONS: Treatment with S1P can inhibit the CTX-induced granulosa cell apoptosis. The S1P protective effect is mediated by activating the PI3K/Akt pathway.