Salvianolic acid A exhibits anti-tumor activity in nasopharyngeal carcinoma cells through regulation of Pin1

Background: Nasopharyngeal carcinoma (NPC) remains as a devastating malignancy due to a lack of effective therapy for recurrence and metastasis. Salvianolic acid A (SAA), a compound extracted from Salvia miltiorrhiza, possesses a variety of biological properties such as antioxidant, antithrombotic, myocardial ischemia protection and anti-hepatic-fibrosis. However, the effect of SAA on NPC cells has not been clarified yet. Methods: NPC cell lines and immortalized nasopharyngeal epithelial cells NP69 were treated with SAA at different concentrations (0-40 μM). Series of relevant experiments were carried out to test the effect of SAA on the proliferation and migration ability of NPC and NP69 cells Pull-down assay and Western blot were used to find out the possible molecular target of SAA. Results: Our results indicated that SAA could inhibit the proliferation of NPC cells in a dose and time dependent manner. And SAA was able to weaken the clone-forming ability as well. Meanwhile, the migratory and invasive capabilities were also attenuated. Moreover, SAA didn’t exhibit any cytotoxicity on immortalized nasopharyngeal epithelial NP69 at the same treatment condition. Furthermore, high concentration of SAA could promote the apoptotic of CNE2 and HNE1 cells dramatically. The results of in vitro pull down assay showed that SAA might bind with Pin1 directly. And the results of western blot indicated that SAA could down-regulate the expression level of cyclin D1, p53, p21 and Bcl-2, which are downstream substrates of Pin1. Conclusions: SAA exhibits anti-tumor activity in NPC through down-regulating Pin1 and it may be a potential drug for NPC.