Isocorydine inhibits the proliferation of human endometrial carcinoma HEC-1B cells by downregulating the Ras/MEK/ERK signaling pathway

Objective: Isocorydine (ICD), an aporphine alkaloid, plays a role in anticancer activity that is still being evaluated. However, the exact function and mechanism of ICD in endometrial carcinoma is largely unknown. Methods: MIT, flow cytometry, western blot, immunofluorescence, RT-PCR and ELISA were used in this research. Results: In our study we showed that ICD inhibited endometrial carcinoma HEC-1B cell proliferation at certain times and concentrations. Simultaneously, ICD induced HEC-1B cells apoptosis. Further investigation indicated that ICD reduced the phosphorylation protein levels of c-Raf (rapidly accelerated fibrosarcoma), MEK1/2 (MAPK/Erk kinase) and ERK1/2 (extracellular regulated protein kinase). Moreover, a cell immunofluorescence assay confirmed that ICD reduced intracellular expression of Ras and then promoted FOXO3 (forkhead box O-3) nuclear localization to furtherly increase the mRNA level of Bim and p27Kip1. Additionally, an enzyme-linked immunosorbent assay (ELISA) revealed that ICD inhibited the production of EGF (epidermal growth factor) and PDGF (Platelet-Derived Growth Factor), which indicated that ICD indirectly inhibited the activation of the Ras/MEK/ERK signaling pathway at the ligand level. Conclusion: Taken together, these data suggest for the first time that ICD inhibits cell proliferation and induces cell apoptosis in endometrial carcinoma through suppressing Ras/MEK/ERK signaling, which may provide a theoretical foundation to the application of ICD for the treatment of human endometrial carcinoma.