Abstract

To explore the antitumor effects of physcion 8-O-β-glucopyranoside (PG) on cell pyroptosis and metastasis in the human osteosarcoma (OS) cells and its underlying mechanisms of action. Human OS cell lines HOS and SAOS-2 cells were used in the present study. Cell viability was examined by the CCK-8 assay. Matrigel invasion and TUNEL staining assays were used to analyze cell invasion ability and pyroptosis. The expressions of pyroptosis, EMT, NLRP, and ERS-related proteins were assessed by western blot. Xenograft OS mice model was used for the in vivo experiments. Administration of PG (0 μM, 10 μM, 20 μM) significantly reduced the cell viability of the HOS and the SAOS-2 cells, while promoting the pyroptosis of these cells. PG showed a dose-dependent inhibition of the invasion and metastasis of the OS cells. However, inhibition of NLPR3 and the ER stress maker CHOP restored the effect of PG on pyroptosis and cell metastasis, suggesting that the PG-induced antitumor effects on the HOS and the SAOS-2 cells were mediated by the ER stress-activated NLRP3 inflammasome. Further, the in vivo experiments showed that PG reduced both tumor growth and invasion in the xenograft OS mice model. The results provide valuable insight into the possible underlying mechanisms of PG effects in the human osteosarcoma cells which could be used as a potential anticancer drug for OS treatment.

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