Huang Ranxin, Li Xiaolin, Huang Xiaochun, Yang Xiaogang, Li Wenqi
Department of Hematology, Xiangya Hospital, Central South University, Changsha 410008, China.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2009 Jun;34(6):515-22.
OBJECTIVE: To determine the effect of arsenic trioxide combined with adriamycin(ADM) on the proliferation and apoptosis of human lymphoma cells. METHODS: Raji cells were divided into an experimental group and a control group, and the experimental group was further divided into 1 micromol/L As(2)O(3) group,2 micromol/L As(2)O(3) group, ADM group,1 micromol/L As(2)O(3) and ADM group,2 micromol/L As(2)O(3) and ADM group. Human lymphoma cells Raji were treated with As(2)O(3) combined with ADM. Wright-Giemsa dying assay was used to observe the apoptosis morphology of lymphoma cells. The proliferation of the cells treated with As(2)O(3) and adriamycin was detected by the method of 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide(MTT). Flow cytometry(FCM) was used to detect the apoptosis rate of lymphoma and the fluorescene density in the lymphocytes. Effect of arsenic trioxide and adriamycin on the mutant p53 expression in Raji cells was detected by semi-quantitive RT-PCR. RESULTS: Evident apoptotic morphological changes of Raji cells were observed 24 hours after treatment with As(2)O(3) or ADM. Compared with As(2)O(3) or ADM alone, As(2)O(3) combined with ADM could increase the inhibition ratio significantly (P<0.05), and the inhibition rate was related to the concentration and action time of As(2)O(3) (P<0.05). Compared with As(2)O(3) or ADM alone, As(2)O(3) combined with ADM could increase the apoptosis rate of lymphoma cells with obvious difference (P<0.05). Semi-quantitive and RT-PCR showed that the expression of mutant p53 in As(2)O(3) and ADM alone and combined groups was obviously less than that in the control (P<0.05). After the treatment with 1 micromol/L and 2 micromol/L As(2)O(3), the fluorescene density in the Raji cells was 18.53 and 18.12, 0.056 and 0.023 times increase respectively.There was no difference (P>0.05). CONCLUSION: As(2)O(3) and ADM alone or combined can inhibit the proliferation, induce cell apoptosis, and downregulate the expression of mutant p53 in vitro. As(2)O(3) combined with ADM has synergistic anti-lymphoma cell effect in vitro. As(2)O(3) has no significant effect on the concentration of ADM on the Raji cells, but can enhance the chemosensitivity of Raji cells, and its mechanism may be that it can downregulate the expression of mutant p53.
目的：探讨三氧化二砷联合阿霉素（ADM）对人淋巴瘤细胞增殖及凋亡的影响。 方法：将Raji细胞分为实验组和对照组，实验组再分为1 μmol/L As₂O₃组、2 μmol/L As₂O₃组、ADM组、1 μmol/L As₂O₃与ADM联合组、2 μmol/L As₂O₃与ADM联合组。采用三氧化二砷联合阿霉素处理人淋巴瘤细胞Raji。用瑞氏-吉姆萨染色法观察淋巴瘤细胞的凋亡形态。采用3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐（MTT）法检测经三氧化二砷和阿霉素处理的细胞增殖情况。采用流式细胞术（FCM）检测淋巴瘤细胞凋亡率及淋巴细胞内荧光强度。采用半定量RT-PCR检测三氧化二砷和阿霉素对Raji细胞中突变型p53表达的影响。 结果：经三氧化二砷或阿霉素处理24小时后，观察到Raji细胞有明显的凋亡形态学改变。与单独使用三氧化二砷或阿霉素相比，三氧化二砷联合阿霉素可显著提高抑制率（P<0.05），且抑制率与三氧化二砷的浓度和作用时间有关（P<0.05）。与单独使用三氧化二砷或阿霉素相比，三氧化二砷联合阿霉素可明显提高淋巴瘤细胞的凋亡率（P<0.05）。半定量RT-PCR显示，单独使用三氧化二砷和阿霉素及联合组中突变型p53的表达明显低于对照组（P<0.05）。经1 μmol/L和2 μmol/L三氧化二砷处理后，Raji细胞内荧光强度分别增加18.53倍和18.12倍、0.056倍和0.023倍，差异无统计学意义（P>0.05）。 结论：三氧化二砷和阿霉素单独或联合使用均可在体外抑制增殖、诱导细胞凋亡并下调突变型p53的表达。三氧化二砷联合阿霉素在体外具有协同抗淋巴瘤细胞作用。三氧化二砷对Raji细胞中阿霉素的浓度无显著影响，但可增强Raji细胞的化疗敏感性，其机制可能是下调突变型p53的表达。
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2009-6
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2015-10
Zhonghua Xue Ye Xue Za Zhi. 2007-7
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2008-12
Zhonghua Zhong Liu Za Zhi. 2002-7
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2010-10
Zotero 插件