The Effect of Sufentanil on the Malignant Biological Behaviors of Osteosarcoma Cells by Adjusting MAPK/ERK Signaling Pathway

This article mainly discusses the effect of Suf (sufentanil) on malignant biological behaviors of OS (osteosarcoma) cells by regulating MAPK (mitogen-activated protein kinase)/ERK (extracellular signal-regulated kinase) signaling pathway. Human osteosarcoma cells (143B cells) and human osteoblast cell line (hFOB1.19 cells) were treated with gradient concentrations of Suf, and the optimal concentration of Suf was determined by CCK-8 screening. The cultured 143B cells were randomly separated into OS group, Suf low-dose group (Suf-L group), Suf medium-dose group (Suf-M group), Suf high-dose group (Suf-H group), and Suf high-dose + ERK activator isoproterenol group (isoproterenol group). EDU staining, colony formation assay and flow cytometry were used to detect the proliferation and apoptosis of 143B cells in each group. The invasion and migration abilities of 143B cells in each group were detected by Transwell and scratch test. Western blot was used to detect cell proliferation, apoptosis, invasion, migration, and the expression of MAPK/ERK signaling pathway related proteins in each group were detected. In addition, nude mouse tumorigenic experiment was used to observe the effect of Suf on the growth status of osteosarcoma. The results showed that Suf had no statistically significant effect on the viability of hFOB1.19 cells (P>0.05). Suf had cytotoxicity effect on 143B cells, and the concentrations of 20, 40, and 80 ng/mL were selected as the the Suf treatment concentrations in the subsequent experimental groups. Compared with the OS group, The EDU-positive cell rate, clone number and Ki67 expression of 143B cells in the Suf-L, Suf-M and、 Suf-H groups were decreased, and the migration rate, invasion number, VEGF and Vimentin expression were decreased, and p-MEK1/2/MEK1/2, p-ERK1/2/ERK1/2 were decreased. The expressions of survivin was decreased, while the apoptosis rate and Bax expression were increased (P<0.05). Compared with the Suf-H group, the EDU- positive cell rate, clone number and Ki67 expression of 143B cells in the Suf-H+ISO group were increased, and the migration rate, invasion number, VEGF and Vimentin expression were increased, and p-MEK1/2/MEK1/2, p- ERK1/2/ERK1/2 were increased. The expressions of Survivin was increased, while the apoptosis rate and Bax expression were significantly decreased (P<0.05). The results of the nude mice tumorigenesis experiment showed that the growth rate of transplanted tumor in nude mice in the Suf group was slow, and the volume and weight of transplanted tumor were significantly reduced. The expression of p-MEK1/2/MEK1/2 and p-ERK1/2/ERK1/2 in the tumor tissue of nude mice were lower than those in the NC group. The positive rate of Ki67 and VEGF were lower than those in the NC group, and the positive rate of Bax was higher than that in the NC group (P<0.05). In conclusion, Suf can inhibit the malignant biological behaviors of osteosarcoma cells, which may be closely related to the inhibition of the MAPK/ERK signaling pathway.

CSTR: 32200.14.cjcb.2025.12.0015