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Epidermal growth factor receptor substrate 8 vaccine-mediated breast cancer cell growth inhibition and the underlying mechanisms
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Abstract:
Objective : To study the inhibiting effect of a vaccine against epidermal growth factor receptor substrate 8 (EPS8) on the growth of breast cancer cells and the possible underlying mechanisms. Methods: Recombinant mouse EPS8 protein was prepared through gene recombination, expression and purification. A vaccine was generated using this recombinant EPS8 protein and BALB/c mice were immunized with this vaccine (n=8) or an adjuvant (n=8). The titer of anti-EPS8 antibody before and at different time points after immunization was assessed by indirect ELISA. Proportion of T lymphocyte subsets in the spleen of immunized mice was determined through flow cytometry before and after immunization. Seven days after the third immunization with ESP8 vaccine or the adjuvant, mice were injected with 4T1 breast cancer cells. In the two groups of animals, survival time, tumor volume, and tumor weight were assessed and the rate of tumor growth inhibition was accordingly calculated. In tumor-bearing animals, T lymphocyte subsets in the spleen were analyzed by flow cytometry, and CTL killing rate was measured by LDH assay. Results: High levels of Eps8 protein were detected in 4T1 cells. Anti-EPS8 antibody was produced inmice immunized with the EPS8 vaccine; its titer was increasing with the frequency of immunization. Survival time was significantly higher mice (P<0.05), tumor weight was significantly lower (\[2.21±0.35\] g vs \[3.31±0.88\] g, P＜0.05), the proportion of CD4＋T cells and ratio of CD4＋/CD8＋in the spleen were significantly higher (P<0.001), those control animals and the CD4＋CD25＋Treg/CD4＋T cell ratio in the spleen was significantly lower (P<0.001) in mice immunized against ESP8 than in control animals. There was no difference in the percentage of CD8＋ T cells in the spleen between two groups (P>0.05). EPS8 vaccination resulted a significant increase in the killing activity of CTLs as compared with the control (\[19.05±4.41\]% vs \[13.36±310\]%, P<0.05). Conclusion: EPS8 vaccination may induce the mice functional humoral immune response, reduce the proportion of Treg cells, and enhance the cytotoxicity of T cells in mice with breast cancer, thereby suppressing tumor growth and prolong survival.
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Project Supported:
Project supported by the National Natural Science Foundation of China (No. 81372249), the University Doctoral Foundation of Education Ministry (No. 20114433110012), and the Science and Technology Innovation Project of the Education Bureau of Guangdong Province (No. 2012KJCX0025)
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