Study On FAK Signaling Pathway Involved In Invasion And Metastasis Of Human Neuroblastoma By 2,3 - Indole Quinone

Objective: Previous research has shown that isatin has an inhibitory effect for a variety of tumors. Isatin is able to alter the proliferation of human neuroblastoma cells(SH-SY5Y)by blocking cell cycle. The aim of the present study was to investigate invasion and migration of SH-SY5 Y cells and the related molecular mechanism.Methods: SH-SY5 Y cells were treated with isatin at various concentrations(25μmol/L, 50μmol/L, 100μmol/L, 200μmol/L).The migration ability of SH-SY5 Y cells were assessed through transwell migration assays. MMP9 m RNA were analyzed via RT-PCR.The proteins that related were analyzed via western blotting.FAK inhibitor PF-562271 were used in positive control group.Results: After treated with isatin, the migration of SH-SY5 Y cells decreased.RT-PCR and western blotting showed that the expression of MMP9 decreased and there is a decline in the phosphorylation level of FAK(Tyr397), ERK(Thr202/ Tyr204) and Paxillin(Tyr118)both in isatin treated group and positive control group. The phosphorylation level of SAPK/JNK(Thr183/Tyr185) differences were of no significance between isatin treated group and control group,while the phosphorylation level of SAPK/JNK(Thr183/Tyr185) in positive control group were significantly lower,compared with control group.Conclusions: Isatin can inhibit migration and invasion of SH-SY5 Y cells and FAK signal pathway maybe involved in the process. The phosphorylation of FAK was affected by isatin,causing changes of related proteins,which lead to decrease in the expression of MMP9.In this way,the invasion of SH-SY5 Y cells was affected. The phosphorylation of FAK and paxillin was affected,causing negative influence in the reorganization of cytoskeleton,which is important for metastasis. Besides,Cell motility was decreased when phosphorylation of paxillin was affected.