Research On The Mechanism Of Apoptosis By 3u In Human Osteosarcoma Cell U2OS

Cancer incidence and death rates have been significantly reduced by further research into the cancer,through early screening,targeted therapy and prevention measures.However,cancer is still a major threat to human health in the world.Osteosarcoma is a genetically heterogeneous malignancy that predominates in adolescents and children,as well as people over 60 years of age.Although the incidence of osteosarcoma is not as high as lung cancer,breast cancer,colorectal cancer,etc.,it is characterized by rapid growth,easy to produce drug resistance,no effective target,high recurrence rate,easy metastasis,and poor prognosis.The 5-year survival rate for young patients with neoadjuvant chemotherapy is 65 to 70 percent,while the 5-year survival rate for patients with transformational osteosarcoma is less than 30 percent.Early symptoms are few,can be treated by amputation chemotherapy or limb salvage chemotherapy,but can also produce poor prognosis and other symptoms.Only chemotherapy can be used for the invasion and metastasis of osteosarcoma in the middle and late stage.Therefore,it is urgent to develop a specific chemotherapeutic drug with little side effects.1,8-naphthidine derivative is a complex structure consisting of two pyridine rings bonded to two adjacent carbon atoms,with only one nitrogen atom in each ring,and located between the 1 and 8 positions.And it has been paid special attention by researchers because of its various biological activities.1,8-naphthidine derivatives have a wide range of biomedical applications,and can be used in anti-malignant tumors,anti-allergic reactions,bacterial resistance,anti-growth,anti-malaria,antiinflammatory and analgesic agents,as well as in the treatment of hypertension,etc.,providing important protection for human health.Professor Yan Shengjiao from Yunnan University synthesized a series of 1,8-naphthidine derivatives,one of which is 6-p-methylbenzoyl-11-methoxy-1,2,3,4-tetrahydrobenzo [g][1,3] diazepine [1,2a]naphthidine [1,8],or 3u.Studies have found that 3u has low toxicity to human normal cell lines,and has a good killing effect on osteosarcoma cells U2 OS.However,the specific mechanism of action is still unclear.Therefore,this study focuses on the mechanism of 3u inducing osteosarcoma cell death.Apoptotic bodies were observed in 3u treated U2 OS cells under the microscope,and the apoptotic bodies increased with the change of time in a concentrationdependent relationship.Total proteins were extracted from U2 OS cells to detect proteins related to apoptosis pathway,and antagonists of major proteins were added for comparison.The death mode of 3u induced U2 OS cells was further determined by fluorescence staining,flow cytometry and western blotting.In this apoptosis pathway,3u induced apoptosis of U2 OS cells by up-regulating the death receptor DR5,inhibiting the expression of anti-apoptosis proteins c-FLIP and XIAP,and activating the key protein Caspase-3/8 in the apoptosis pathway.In animal models using immunodeficient mice,subcutaneous tumor induction was performed by injecting a cell suspension.After 21 days of administration,the tumor and other tissues of nude mice were observed,and it was found that the growth of osteosarcoma was significantly inhibited by 3u,and no obvious lesion metastasis was observed.In conclusion,compound 3u induced apoptosis of U2 OS cells by up-regulating the death receptor DR5,inhibiting the expression of anti-apoptotic proteins c-FLIP and XIAP,and activating the key protein Caspase-3/8 in the apoptotic pathway.In animal experiments result is good,and no significant lesions.Compound 3u has obvious advantages in the treatment of osteosarcoma and has good potential in the development of proteins related to targeting apoptosis induction.