Effect Of Arsenic Trioxide Combined With Adriamycin On Proliferation And Apoptosis Of Human Lymphoma Cells

Non-Hodgkin's lymphoma is one of heterogeneity hematologic malignant tumors,which is sourced from lymphoid tissue. At present, anthracycline-based regiment is widely used in clinic ,Although it could improve the overal survival rate of lymphoma patients,the treatment evaluation of most patients was poor and remission time was short. Some patients can't tolerance it because of it's serious side effects. Arsenic trioxide(As₂O₃) has shown obvious anti-tumor effect both in vitro and in animal experiments, and the mechanisms are related to cell cycle blocking and apoptosis-inducing effects,etal.It has tolerable side effect and no cross-resistantdrug with other chemodrugs. And domestic and foreign studies suggest that As₂O₃ single or combined other drugs can inhibit proliferation of variety lymphoma cells in vitro.To provide theoretical proof for new curative chemotherapy drugs and combination chemotherapy programs in clinic, we treated human lymphoma cells Raji with As₂O₃ combined with the traditional chemotherapy drug: adriamycin, and observed the changes of the cells proliferation and cells apoptosis rate. Wright-Giemsa dyeing assay was used to observe apoptosis morphology of lymphoma cells. Detecting proliferation of the cells with As₂O₃ combined with adriamycin by the method of MTT. Flow cytometry(FCM) was used to detect apoptosis of lymphoma and the impact of fluorescene density in the cells by arsenic trioxide. The semi-quantitive RT-PCR was used to detect mutant p53 expression in Raji cells. The results showed that evident change of apoptosis morphology was found in Raji cells after treatment with As₂O₃ and ADM 24 hours. Compared with using alone, the combination of the two drugs can increase the inhibition rates more obviously(P<0.05), and the inhibition rate was related to the concentration and acting time of As₂O₃ (P<0.05). As₂O₃ combined with adriamycin can increase the apoptosis rates of lymphoma cells , and there is obviously difference(P<0.05) ,compared with the two drugs alone. The semi-quantitive RT-PCR showed that the expression of mutant p53 of using alone and combined groups was obviously less than the control(P<0.05). When disposed with 1μmol/L and 2μmol/L As₂O₃, the fluorescene density in Raji cells is 18.53 and 18.12 respectively,increasing 0.056 and 0.023 times respectively,the evident defference of fluorescene density of ADM in the cells not existing by stastically analysizing(P>0.05).In conclusion, As₂O₃ and ADM using alone or combined can inhibit Raji cells proliferation, induce cells apoptosis and downregulate the expression of mutant p53 in vitro. As₂O₃ combined with adriamycin has synergistic effects on Raji cells in vitro. As₂O₃ cann't increase the concentration of ADM in the Raji cells. As₂O₃ can enhance chemosensitivity of Raji cells by downregulating the expression of mutant p53.