Study On The Mechanisms Of PAK5 Participation In The Invasion,Metastasis And Drug Resistance Of Osteosarcoma

BACKGROUND:Osteosarcoma is the most common primary malignant bone tumors,the annual incidence of 0.2 ~ 0.3/100,000.Osteosarcoma mainly occurs in teenagers,onset ages 5 to 20 years old.Main location in long bone,generally in distal femur or proximal tibia,followed by proximal humeral,other parts is rare.The blood metastasis occurs early and progress rapidly,the metastasis area is mainly located in the lungs.1970 years ago,limb osteosarcoma generally was treated by amputation surgery,its five-year survival rate was less than 20%,and the main reason of death was pulmonary metastasis.The application of chemotherapy obviously decreased osteosarcoma patients' pulmonary metastasis rate,and 5-year survival rate increased from 60% to 80%.But there have a part of patients to produce drug resistance and lead to relapse or metastasis,which cause the final treatment failure and death.Many factors are involved in the occurrence and development of osteosarcoma,the development of osteosarcoma is a multi-step biological process.Insight into recurrence and metastatic mechanism is of great significance for finding the ideal therapeutic targets.P21 activated kinase 5(p21-activated kinase 5,PAK5)is PAKs newly discovered member of the family,which plays an important role in the cytoskeleton reorganization,cell growth,proliferation,differentiation,gene transcription and cell apoptosis,and a series of cellular functions.In recent years,some studies have found that p21 activated kinase 5 protein has some closely relations to the invasion and metastasis of malignant tumor,such as breast cancer,colon cancer,etc.But its role in osteosarcoma remains unclear.OBJECTIVE:To explore the PAK5 role in pulmonary metastasis and drug resistance of osteosarcoma.METHODS:Using immunohistochemical method detects PAK5 expression in osteosarcoma tissues and pulmonary metastasis tissues,and analyzing the relationship between PAK5 expression and clinical parameters such as patient gender,age,disease,pathological type,Enneking surgical stage,tumor necrosis rate,with or without pulmonary metastasis,the median progression-free survival.Using QRT PCR,western blot and immunofluorescence s detect the PAK5 expression in osteosarcoma cells.Using drug sensitivity experiment,cell proliferation,scratch and Transwell invasion chamber test analyze PAK5 role of invasion and metastasis in osteosarcoma cells.RESULTS:PAK5 in osteosarcoma and lung metastasis tissue is positive expression while PAK5 in normal tissue of bone is negative expression.PAK5 protein has obvious correlation with the effective of chemotherapy,disease prognosis and osteosarcoma pulmonary metastasis.PAK5 silencing in MG63 and Saos2 cells reduced IC50 and induce cell apoptosis,and the dose-depedent in tumor cells.PAK5 silencing in osteosarcoma cells could weaker proliferation transfer capacity significantly than not silence PAK5 migration of osteosarcoma cells.PAK5 and MMP2 has high expression in osteosarcoma pulmonary metastasis tissues.PAK5 has correlation with tumor metastasis related genes,expecially MMP2.CONCLUSIONS:.PAK5 play a role in the invasion and metastasis of osteosarcoma,and may participate in the regulation of osteosarcoma chemotherapy drugs sensitivity.