The role and the molecular mechanism of abietic acid in the proliferation,invasion and migration of cisplatin-resistant nasopharyngeal carcinoma cells
Objective:To investigate the effects and molecular mechanisms of abietic acid in the cell prolifera-tion,invasion and migration of cisplatin-resistant nasopharyngeal carcinoma cells.Methods:①Cisplatin-resistant C666/DDP cell line was constructed by increasing drug concentration method.②The effects of abietic acid on pro-liferation,invasion and migration of C666/DDP cells were investigated by CCK-8 method,reactive oxygen species(ROS)and mitochondrial membrane potential(MMP)level assay and subcutaneous tumorigenesis assay in nude mice to detect the effects of abietic acid on proliferation and apoptosis of C666/DDP cells in vitro and in vivo.The effect of abietic acid on the proliferation and apoptosis of C666/DDP cells in vitro and in vivo was measured by Tr-answell assay.③Western blot and IHC method to detect the expression of PI3K/AKT/mTOR pathway related proteins.Results:①The IC50 of cisplatin cytotoxicity to C666-1 was about 25 μmol/L.RI=25 µmol/L/4 μmol/L=6.25,resistance was obtained,and the C666-1-DDP resistant strain was successfully constructed.②Abietic acid promoted apoptosis and inhibited proliferation of C666/DDP cells,and showed G2/M phase block;transwell showed that abietic acid inhibited C666/DDP cell migration and invasion,increased ROS level of C666/DDP cells and decreased MMP.Transwell showed that abietic acid inhibited the migration and invasion ability of C666/DDP cells,increased the ROS level of C666/DDP cells and decreased MMP.③Animal experiments showed that abietic acid inhibited the proliferation of cisplatin-resistant nasopharyngeal carcinoma in vivo in a concentration gradient and suppressed the expression of PI3K/AKT/mTOR signaling pathway-related proteins.Conclusion:Abietic acid inhibits proliferation,invasion and migration of cisplatin-resistant nasopharyngeal carcinoma cells by a mechanism related to inhibition of PI3K/AKT/mTOR signaling pathway.
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