Treatment efficacy of MUC1-DC vaccine in breast cancer MCF-7 cell xenografts in nude mice evaluated by monitoring tumor growth with optical molecular imaging
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Abstract:
Objective: To evaluate the treatment efficacy of mucin 1 (MUC1) gene transfected dendritic cell (MUC1-DC) vaccine on breast cancer MCF-7 cell xenografts in nude mice and its possible mechanism. Methods: GFP lentivirus were transfected into human breast cancer MCF-7 cells to obtain the GFP-MCF-7 cells which were subcutaneously implanted into BALB/c nude mice. After tumorigenesis, the mice were randomly divided into three groups. First, CIK cells activated in vitro (1×108 cells/mouse) were injected into the mice of each group via tail vein. In the treatment groups, MUC1-DC (MUC1-DC group) or DC (DC group) were injected subcutaneously (0.2 ml, 1×107 cells/mouse). In the control group, normal saline of the same volume was injected. The treatment frequency was once per day for 5 consecutive days. The fluorescence imaging of transplanted tumor was observed before and 35 days after the treatment with optical imaging system, and fluorescence intensity and area were analyzed. The expression of Caspase 3 in xenograft tissues was detected by immunohistochemistry, and the cell apoptosis was detected by TUNEL assay. Results: The tumor formation rate of nude mice was 100% at 7 days after GFP-MCF-7 implantation. The results of optical molecular imaging showed that there was no significant difference in fluorescence signal intensity among MUC1-DC group, DC group and Control group before treatment (P>0.05). At day 35 after treatment, the fluorescence signal intensity of MUC1-DC group and DC group was significantly lower than that of Control group (P<0.05). There was no significant difference between DC and Control group, as well as between MUC1-DC and DC group (all P>0.05), but the fluorescence signal of MUC1-DC group was lower than that of DC group. There was no significant difference in the distribution area of fluorescence signal among MUC1-DC group, DC group and Control group before treatment (P>0.05). At day 35, the fluorescence signal in Control group was scattered in multiple areas, and the area of fluorescence signal in MUC1-DC group and DC group was significantly smaller than that in Control group (all P<0.01), but there was no significant difference between MUC1-DC group and DC group (P>0.05). Caspase 3 expression was the highest in MUC1-DC group, followed by DC group, and the least in Control group, and the differences among the three groups were significant (all P<0.05). TUNEL results showed that the apoptosis rate of Control group, DC group and MUC1-DC group was (4.11±2.61)% , (9.63±2.27)% , and (25.30±8.24)% , respectively (all P<0.05). Conclusion: Compared with mere DC immunotherapy, MUC1-DC vaccine can more effectively inhibit tumor growth and metastasis in nude mice bearing human breast cancer cell xenografts, exerting a better effect in promoting tumor cell apoptosis.
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Project supported by the Program of Scientific Research Foundation from Health and Family Planning Commission of Dalian City(No.2012-0407L)