The Effect Of Curcumin On Proliferation And Metabasis Of Osteosarcoma And Its Related Mechanisms

Background&Objective:Osteosarcoma is the most common primary bone tumor,mainly affecting children and adolescents.As it is difficult to diagnosis earlily and prones to metastasis,5-year survival rate for osteosarcoma patient is very low.Hence,it is of importantance and urgency for us to understand the pathogenesis of osteosarcoma and seek better treatment program.Surgery combined with adjuvant chemotherapy is the most commonly used treatment for osteosarcoma.Thanks to the rapid development of adjuvant chemotherapy,its 5-year survival rate has increased;However,a number of side effects have been reported for the currently used chemotherapeutic agents,including marrow suppression,visceral toxicity,etc..It is therefore necessary to seel novel anti-tumor drug with low toxicity.As the main active ingredient of dried turmeric,curcumin possess its major pharmacological effects,including anti-inflammatory,anti-diabetic,and neuroprotective.Curcumin also plays an important role in regulating proliferation and metastasis of tumor.What is more,it is nontoxic for the human body.However,it remins unknown about its effect on osteosarcoma and the underlying molecular mechanism.EZH2(enhancer of zeste homolog 2)can maintain the cell proliferation,differentiation,cell cycle,metastasis and drug tolerance.It has been found that EZH2 is rarely expressed in healthy tissues,but highly in tumor tissue,such as prostate cancer and breast cancer.It is also reported that EZH2 was associated with tumor progress,indicating EZH2 may be the target gene of tumor treatment.Evidence suggests that curcumin can affect tumor cell proliferation and apoptosis via regulating the expression of EZH2.Recently,EZH2 was revealed to be expressed in osteosarcoma.However,there is few study exploring its effect on the development and progress of osteosarcoma and related mechanisms.miRNA is a class of non-coding protein single-stranded small RNA molecules,usually affecting the proliferation and migration of tumor by binding 3 'UTR of target gene.miRNA-138 has been studied in colon cancer,lung cancer,cholangiocarcinoma,and plays a tumor suppression role for these tumor.However,the role of miRNA-138 in osteosarcoma cells and the changes of miRNA-138 expression in osteosarcoma cells treated with curcumin are not fully understand.Therefore,we conducted this study to investigate the effect of curcumin on the prolifetaion and migraton of osteosarcoma,and investigated the role of miRNA-138/EZH2 on it.Methods&Content:This project comprises of four parts:1.To investigate the effect of curcumin on the proliferation of osteosarcoma,migration and apoptosis,and check the expression of EZH2 and miRNA-138 in osteosarcoma treated with curcumin.2.To investigate the role of miRNA-138 in regulating the proliferation and apoptosis of osteosarcoma.3.To explore the target gene of miRNA-138 and verify its effect.4.To testify wethter curcumin regulate the proliferation and migration of osteosarcoma cells via targeting miRNA-138/EZH2.Results:Our results showed that the expression level of miRNA-138 in osteosarcoma was decreased,and miRNA-138 could regulate EZH2 to regulate the proliferation,migration and apoptosis of osteosarcoma cells.Curcumin could inhibit the proliferation of osteosarcoma by reducing the expression of EZH2,and this effect was regulated by upregulating miRNA-138.Conclusion:Curcumin could inhibit the proliferation of osteosarcoma by regulating EZH2.Curcumin inhibited the proliferation?migration and promoted the apoptosis of osteosarcoma via targeting miRNA-138/EZH2 pathway.