转染CD40配体的卵巢癌细胞株OVHM抗卵巢癌肝转移机制的研究

Objective To examine the in vivo anti-metastatic effect of enhanced expression of CD40L cDNA in murinc ovarian cancer OVUM cells (CD4OL-OVHM) injected into the spleen on liver metastasis in mice. Methods OVUM cells were inoculated into the spleen of 6 ～ 8 week-old female B6C3F1 (C57BL/6N × C3H/He) mice. The established liver metastasis was identified by histopathology (HE staining). OVUM cells, DNA-pMKITneo-OVHM cells or CD40L-OVHM cells were inoculated into the spleen of female B6C3F1 mice and the expressions of CD11c in splenic cells were detected by flow cytometry. The specific cytotoxicity of splenic cells was detected by MTT assay, and the serum cytokines of IFN-γ, TNF-α, IL-12, IL4 and IL-10 of the mice were measured by enzyme linked immunoabsorbent assay. The liver metastases and the survival time of the mice were also recorded. Results The mouse models with liver metastasis by injecting tumor cells into the spleen of mice were established. The expression of CD11c and the specific killing rote in CD40L-OVHM cells group was significantly higher than that in the OVHM cells group and DNA-pMKITneo-OVHM cells group. The expressions of IFN-γ, TNF-α and IL-12 in the CD40L-OVHM cells group were much more increased than OVHM cells group and DNA-pMKITneo-OVHM cells group, but the expressions of IL-4 and IL-10 in the CD40L-OVHM cells group were decreased significantly (P < 0.05). The average weights of livers and spleens of mice in CD40L-OVHM cells group were significantly lower than those of DNA-pMKITneo-OVHM cells group and OVHM cells group. The survival time of mice in CD40L-OVHM cells group was also significantly longer than that in the OVHM cells group and DNA-pMKITneo-OVHM cells group (P < 0.05). Conclusion The data directly demonstrate that the expression of CD40L in ovarian cancer cells (CD40L-OVHM) can enhance the proliferation and differentiation of dendritic cells in the spleen and induce specific cytotoxic effect of T cells in the spleen, and may regulate the immune function of peripheral blood cells and the immune balance between Thl cells and Th2 cells, which maybe the possible mechanism induced by CD40L in mice inhibiting the development of liver metastasis.

Inhibitory effects of enhanced expression of CD40L in ovarian cancer OVHM cells on the liver metastases in mice