Effects of evodiamine on PI3K/Akt and MAPK/ERK signaling pathways in pancreatic cancer cells

The effective antitumor drug evodiamine (EVO) is attracting increased attention. Therefore, the present study aimed to investigate the effects of EVO on the proliferation, apoptosis and autophagy of human pancreatic cancer (PC) cell lines in vitro and in vivo. Human PANC1 and SW1990 PC cell lines were treated with different concentrations of EVO and proliferation was detected using a Cell Counting Kit (CCK)8 assay. Colony formation and woundhealing assays showed that EVO inhibited PC cell viability and migration, and apoptosis was detected using flow cytometry. Western blotting and immunofluorescence detected the expression of proteins in PANC1 and SW1990 cells. The PANC1 cells were used to establish an orthotopic pancreatic tumor model in nude mice. Tumorbearing nude mice were administered with different concentrations of EVO, and growth was monitored. Highresolution positron emission tomography and fluorine18labeled fluorodeoxyglucose were used to monitor the tumor/nontumor (T/NT) ratio and standard uptake value (SUV) of the mice, which were subsequently sacrificed to measure the transplanted tumor weight. Apoptosis increased with increasing EVO concentration. The EVOtreated PC cells exhibited significantly higher expression of LC3II than the controls cells. EVO decreased LC3II, enhanced P62 and inhibited the expression of Akt, extracellularsignalregulated protein kinase (ERK)1/2 and p38. Compared with the control group, the T/NT ratio, SUV and tumor weight decreased more markedly in the EVOtreated group. The tumor expression of phosphorylated AKT, detected using immunohistochemistry, decreased with increasing EVO doses in vivo. EVO induced PC cell apoptosis by inhibiting phosphoinositide 3kinase/AKT and mitogenactivated protein kinase/ERK and inhibiting the phosphorylation of signal transducer and activator of transcription activator 3 in PC cells to inhibit autophagy, suggesting that EVO may be considered as a novel PC treatment.