Anti-osteosarcoma Effect Of Morusin And Its Mechanism

Background and Aims:Osteosarcoma is the common primary malignant tumor of bone in children and adolescents.The incidence of osteosarcoma is 4-5cases per million population.There is no significant difference between races.At present,cisplatin(DDP),adriamycin(ADM),and methamterine(MTX)are still the main chemotherapeutic drugs in the treatment of osteosarcoma.Although chemotherapy has significantly improved the prognosis of osteosarcoma patients and has made some progress in the treatment of osteosarcoma in recent years,the 5-year survival rate of osteosarcoma patients is still about 60%in the last two decades.In the past 20 years,new chemotherapeutic drugs have emerged,for example,lung cancer has improved significantly with the use of new drugs.However,few new anti-osteosarcoma drugs have been found,and new drugs have been found to be more toxic.Therefore,it is an important research topic in the treatment of osteosarcoma to develop new high-efficiency and low-toxicity drugs for better anti-osteosarcoma.Morusin,a flavonoids isolated from the root bark of mulberry(morus alba)and other mulberry plants,has a variety of biological activities,including anti-inflammatory,anti-virus,anti-cancer effects and so on.However,the antineoplastic effect of mulberry on osteosarcoma is not clear.Methods:(1)in vitro experiment:human osteosarcoma saos2 cells were obtained at logarithmic growth stage.The blank group and the Morusin group with different concentration were set up.The effect of Morusin on cell proliferation was analyzed by MTS assay.The expression of apoptosis related genes mRNA(Bax,Bcl-2,etc.)was analyzed by real-time PCR and Bax/Bcl-2value was calculated to clarify the effect of Morusin on apoptosis.The specific role of Morusin in promoting apoptosis of SAOS2 cells was directly detected and analyzed by ELISA assay.he effects of Morusin on cell migration and invasion were analyzed by transwell assay and scratch test.(2)in vivo experiment:the effect of Morusin on the xenograft model of BALB/c-nu/nu in nude mice was studied.The success rate of the model was 100%when the cells were inoculated into the subcutaneous area near the right shoulder armpit of the back with the concentration of 4×10~6/0.1 ml cells,and the success rate of the model was 100%.Morusin 50 and 25 mg/kg,were intraperitoneally injected once a day for 28 days.Morusin had no visible toxicity to nude mice.During administration,the diameter of the tumor was measured every 3 days.Results:(1)the results in vitro showed that the cell proliferation inhibition rate,relative expression of anti-apoptotic gene,relative migration and invasion ability of Morusin group were significantly lower than those of blank group,and the cell proliferation and anti-apoptotic gene expression of Morusin group were significantly lower than those of control group.And the ability of migration and invasion was inhibited in a concentration-dependent manner.Morusin promoted the relative expression of apoptotic genes and the direct apoptosis of cells.(2)the results in vivo showed that Morusin could significantly inhibit the transplantation of SAOS2 tumor without any visible toxicity to nude mice.Conclusion:Morusin has significant anti-osteosarcoma effect in vitro and in vivo,suggesting that Morusin has certain clinical application value and development prospect.