Neuroblastoma is the most common tumor diagnosed in children and infants, with high recurrence and poor prognosis. Angelica sinensis polysaccharide (AP) whose average molecular weight is 72,900 Da possesses various bioactivities. We aimed to explore the effects of AP on neuroblastoma SH-SY5Y cells as well as the underlying mechanisms. Effects of AP on cell viability, proliferation, apoptosis, migration, invasion, and expressions of long noncoding RNA H19 (lncRNA-H19), microRNA (miR)-675, and CD44 were assessed. Then, effects of miR-675 overexpression on AP-treated cells were analyzed. Next, expression of key kinases in the PI3K/AKT and JAK/ STAT pathways was detected. The possible target gene of miR-675 was finally explored. Cell viability was reduced by 200-500 µg/mL AP. Meanwhile, AP repressed cell proliferation, migration, and invasion, but induced apoptosis. Expressions of lncRNA-H19 and miR-675 were upregulated in neuroblastoma cells, and were downregulated by AP. AP was also identified to upregulate CD44. We next found AP affected SH-SY5Y cells through downregulating miR-675. Key kinases in the PI3K/AKT and JAK/STAT pathways were downregulated by AP stimulation, while these downregulations were abrogated by miR-675 overexpression. KIF1B isoform β (KIF1Bβ) is proved to be a target of miR-675. In conclusion, AP was first identified to inhibit proliferation, migration, and invasion but induce apoptosis. Furthermore, AP might repress tumorigenesis of SH-SY5Y cells through miR-675-mediated inactivation of the PI3K/AKT and JAK/STAT pathways. Besides, KIF1Bβ might be a target of miR-675.

Neuroblastoma (NB) is a serious disease with high-risk and poor prognosis in children. Survivors often have serious side effects. Angelica polysaccharide (AP) has been proved to exert antitumor function. Therefore, we explored the mechanism of this function in NB to accelerate the clinical application of AP in NB therapy. SH-SY5Y cells were transfected with miR-205 inhibitor and pretreated by AP. Cell activity, colonies number, and apoptosis were detected via Cell Counting Kit-8 assay, colony formation experiment, and flow cytometry, respectively. Targeting link between miR-205 and zinc finger E-box binding homeobox 1 (ZEB1) was measured via luciferase activity assay. Quantitative reverse transcription polymerase chain reaction and western blot was to examine levels of miR-205 and related factors. We found that AP suppressed cell activity and colony formation, whereas induced apoptosis in SH-SY5Y cells. Besides, AP also suppressed Epithelialmesenchymal transition process and phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) and extracellular signal-regulated kinase (ERK1/2) signal passageways. Additionally, miR-205 was positively regulated by AP. AP played its antitumor functions through up-regulating miR-205. Target of miR-205 was ZEB1. Our study demonstrated that AP played its antitumor role in NB through positively regulation of miR-205, whose target gene was ZEB1.

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