Effects of Allocryptopine on the Proliferation and Epithelial-Mesenchymal Transition of Oral Squamous Cell Carcinoma through m6A Mediated Hedgehog Signaling Pathway.

Abstract

BACKGROUND Allocryptopine is an isoquinoline alkaloid extracted from Macleaya cordata. This study aimed to explore the effects of allocryptopine on the growth and metastasis of oral squamous cell carcinoma (OSCC) cells. METHODS The human OSCC cell line HSC-3 and SAS were selected in this study. MTT assay was performed to measure cell viability. Western blot was used to detect protein expressions. transwell assay was conducted to determine the migrated and invaded cells. M6A modification was confirmed by methylated RNA immunoprecipitation assay. RESULTS Compared with the NC group, the cell viability, migration and invasion ability of OSCC cells were suppressed after allocryptopine treatment in a dose dependent manner. Allocryptopine upregulated the E-cadherin expression and downregulated N-cadherin and Vimentin expressions in the OSCC cells. In addition, the protein expressions of patched receptor 1 (PTCH1), smoothened co-receptor (SMO) and Gli family (GLI1) were downregulated after allocryptopine treatment. Furthermore, allocryptopine treatment decreased the expression of Methyltransferase like 3 (METTL3) and inhibited N6-methyladenosine (m6A) modification of PTCH1. Moreover, overexpression of PTCH1 reversed the effects of allocryptopine and induced the aggressiveness of OSCC cells. CONCLUSION Allocryptopine suppressed the proliferation and epithelial-mesenchymal transition (EMT) of OSCC cells via m6A mediated Hedgehog signaling pathway, relieving the carcinogenic behaviors of OSCC.