Effects Of Doxorubicin On Apoptosis And Expressions Of NF-?B And P-gp In Human Osteosarcoma U2-OS Cells

Objective:Osteosarcoma is the most common primary malignant bone tumors in children and adolescents,high grade and distant metastasis early,aggressively and poor prognosis.Nowadays,in addition to the traditional surgical treatment,the treatment of osteosarcoma is based on neoadjuvant chemotherapy-based comprehensive treatment,of which chemotherapy is one of the main means.The drugs used for the chemotherapy of osteosarcoma mainly include doxorubicin,cisplatin,methotrexate and ifosfamide.In the process of tumor treatment,the emergence of multi-drug resistance is a major obstacle to the effect of chemotherapy.Studies have shown that,NF-?B is also closely related to multi-drug resistance of tumor cells in addition to involving in inflammation,immunity and stress.In-depth study of transcription factor NF-?B in the occurrence and development of multi-drug resistance of osteosarcoma is of great significance in tne development of targeted drugs and improving the efficacy and survival rate of patients with osteosarcoma.In this study,we observed the effects of doxorubicin on the apoptosis of human osteosarcoma cells and the expression of NF-?B and P-gp protein,and discussed the mechanism of drug resistance.To provide theoretical basis and experimental basis for further study on the reversal of drug resistance in osteosarcoma chemotherapy.Methods: The human osteosarcoma U2-OS cell line was cultured in vitro.The human osteosarcoma U2-OS cells were treated with doxorubicin at 0,1,5,10 and 100 ug / ml for 24 h,48h and 72 h,respectively.Absorbance was detected by MTS method to analyze the effect of doxorubicin on the growth of osteosarcoma U2-OS cells.The apoptosis rate of osteosarcoma U2-OS cells was analyzed by flow cytometry.Western blot was used to detect the expression of NF-?B and P-gp in osteosarcoma U2-OS cells after treated with doxorubicin at different concentrations for 24 h and analyze the possible mechanism of doxorubicin-induced multidrug resistance in osteosarcoma cells.Results: Doxorubicin could inhibit the proliferation of human osteosarcoma U2-OS cells in vitro(P <0.05),and its inhibitory rate increased with the doxorubicin concentration in a time-and dose-dependent manner.Doxorubicin could induce the apoptosis of U2-OS cells(P <0.05),and the apoptosis rate increased with doxorubicin concentration in a time-and dose-dependent manner.Meanwhile,Western blot analysis showed that after treated with doxorubicin at different concentrations for 24 h,the expression of NF-?B and P-gp protein gradually increased(P <0.05)with the concentration of doxorubicin.Conclusion: Doxorubicin can inhibit the proliferation and induce the apoptosis of human osteosarcoma U2-OS cells.At the same time,doxorubicin can up-regulate the multidrug resistance of human osteosarcoma U2-OS cells,which may be related to the expression of NF-?B activated by doxorubicin.