The inhibitory effect of cisplatin combined with tunicamycin on neuroblastoma and related mechanism

Abstract

Objective To investigate the inhibitory effect of cisplatin (DDP) combined with tunicamycin (TM) on human neuroblastoma SH-SY5Y and SK-N-SH cells and related mechanism. Methods Human neuroblastoma SH-SY5Y and SK-N-SH cells were divided into control group, TM group (treated with 0.4 mg/L TM for 24 h), DDP group (treated with 4 mg/L DDP for 24 h), and DDP+TM group (treated with 0.4 mg/L TM and 4 mg/L DDP for 24 h). CCK-8 assay, plate colony formation assay, scratch assay, and Transwell assay were used to measure the viability and proliferation, migration, and invasion abilities of cells in each group, and Western blotting was used to measure the expression levels of the JAK2-STAT3-HIF1α pathway-related proteins such as JAK-2, p-JAK2, STAT3, p-STAT3, and HIF1α in each group of cells. Results Experimental results showed that compared with the other three groups, the DDP+TM group had significantly lower viability, proliferation and invasion abilities, migration ability at 12 and 24 h, and expression levels of the JAK2-STAT3-HIF1α pathway-related proteins (tLSD=2.14-78.95,P<0.05). Conclusion DDP combined with TM can inhibit the proliferation and migration of neuroblastoma via the JAK2-STAT3-HIF1α pathway, which provides new ideas for the treatment of neuroblastoma.

Keywords

• neuroblastoma|cisplatin|tunicamycin|janus kinase 2|stat3 transcription factor|hypoxia-inducible factor 1, alpha subunit|cell movement|cell proliferation