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OBJECTIVE@#To investigate the effect of β-arrestin1 overexpression on tumor progression in a NCG mouse model bearing T-cell acute lymphocytic leukemia (T-ALL) Molt-4 cell xenograft.@*METHODS@#Molt-4 cells were tagged with firefly-luciferase (F-Luc) by lentiviral infection, and fluorescence intensity of the cells was detected using a luminescence detector. Molt-4 cell lines with β-arrestin1 overexpression or knockdown were constructed by lentivirus infection and injected the tail vein in sub-lethal irradiated NCG mice. Body weight changes and survival time of the xenografted mice were observed, and the progression of T-ALL in the mice was evaluated using an fluorescence imaging system. Sixteen days after xenografting, the mice were euthanatized and tumor cell infiltration was observed in the slices of the liver and spleen.@*RESULTS@#We successfully tagged Molt-4 cells with F-Luc and overexpressed or knocked down β-arrestin1 in the tagged cells. Bioluminescent imaging showed obvious luminescence catalyzed by F-Luc in Molt-4 cells. After injection of Molt-4-Luc cells into irradiated NCG mice, a gradual enhancement of luminescence in the xenografted mice was observed over time, while the body weight of the mice decreased. Compared with the control mice, the mice xenografted with β-arrestin1-overexpressing Molt-4 cells had significantly prolonged survival time ( < 0.001), while the survival time of the mice xenografted with Molt-4 cells with β- arrestin1 knockdown was significantly shortened ( < 0.001). Histological examination revealed fewer infiltrating tumor cells in the liver and spleen of the mice xenografted with β-arrestin1-overexpressing Molt-4 cells in comparison with the mice bearing parental Molt-4 cell xenografts.@*CONCLUSIONS@#β-arrestin1 overexpression suppresses tumor progression in mice bearing Molt-4 cell xenograft.
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Animals , Humans , Mice , Disease Progression , Heterografts , T-Lymphocytes , Transplantation, Heterologous , beta-Arrestin 1ABSTRACT
Objective To investigate the effect of bortezomib combined with doxorubicin on lymphoblastic lymphoma cell line Molt-4.Methods Molt-4 cells were cultured in the presence of bortezomib and doxorubicin,cell viability was monitored by CCK-8 and trypan-blue exclusion.Apoptosis was detected by flow cytometry and mitochondrial membrane potential,expression of Fas was also measured with flow cytometry.Results Molt-4 cell proliferation was substantially inhibited in concentration-dependent manners when treated with either bortezomib or doxorubicin.The combination of both drugs synergistically inhibited Molt-4 cell proliferation at 48 hours [(57.24±0.10) ％].Combination therapy further enhanced bortezomib and doxorubicin induced apoptosis [48 h (23.08±1.25) ％] (P ＜ 0.05).Detection of mitochondrial membrane potential showed that combination therapy could promote apoptosis (15.84 ％,5.38 ％,5.52 ％) but did not significantly change the level of Fas expression (P ＞ 0.05).Conclusion Combination therapy of bortezomib with doxorubicin efficiently inhibits proliferation and induces apoptosis of Molt-4 cells.Activation of mitochondrial and intrinsic apoptotic pathway may play important roles.
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Objective To investigate the possible mechanism of apoptosis effect induced by resveratrol in human acute T lymphoblast leukemia Molt-4 cells. Methods MTT method was used to analyze the inhibition rate. The cell cycle and apoptosis percentage of Molt-4 cells treated with resveratrol were detected by flow cytometry. The expression of WAVE1 mRNA was assessed by semi-quantitative RT-PCR. Results After treated with 12.5, 25.0, 50.0, 100.0, 200.0μmol/L resveratrol for 24, 48 and 72 hours, the inhibitory effects were at 29.32 %, 36.11 %, 53.92 %, 62.50 %, and 74.98 %, respectively. Resveratrol was able to inhibit the proliferation of Molt-4 cells in a time-dependent and dose-dependent manner (F =33.614, P <0.05).Compared with control group, after treated with 50.0, 100.0 μmol/L resveratrol for 48 h, the cell number in S phase of Molt-4 cells was 68.6 % and 78.1 %, respectively, and the cell cycle was arrested at S phase (F = 19.453, P < 0.01) after treated with 50.0, 100.0 μmol/L resveratrol for 48 h, the ratio of WAVE1/GAPDH was 0.356±0.03, 0.382±0.05. Compared with control group 0.586±0.06, the ratio of WAVE1/GAPDH was decreased (F =8.950, P <0.01). Conclusion Resveratrol could induce the cells to undergo apoptosis, which was probably related to downregulation the expression of WAVE1.
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to the changes of pro-proliferation genes and anti-apoptosis genes.
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Objective To investigate the effect of Mlot-4 cells onset with Roscovitine (ROSC)as some Cyclin-dependent kinases(CDK),inhibitor.Methods The logarithmic growth phase Molt-4 cells treated with ROSC at a final concentration ranging between 1～20 μmol/L and harvested in different time point,DNA assay of single cells by flow cytometry was used to detect the effect of cell cycle arrest and Annexin-V/FITC assay was used to detect the effect of cell apoptosis. Results It showed that ROSC exerted strong inhibitory effect on proliferation and cell cycle progression of Molt-4 Accumulation of G2/M arrested cells starting 6 h after onset of 10 μmol/L and 20 μmol/L ROSC;at the same time,the cell apoptosis of Molt-4 would be detected,According with the time and concentration changing,the cell apoptosis rate would rise.Conclusion It is concluded that Roscovitine(ROSC)as some Cyclin-dependent kinases(CDK),inhibitor,It has dual effects to Molt-4 cells,not only the effect of cell cycle arrest but also the effect of cell apoptosis.