Fully phosphorothioate-modified CpG ODN with PolyG motif inhibits the adhesion of B16 melanoma cells in vitro and tumorigenesis in vivo.

Abstract

Adhesion to the extracellular matrix and endothelial lining of blood vessels is critical for tumor cells to grow at original or metastatic sites. Inhibition of tumor cell adhesion can be an antitumor strategy. Guanosine-rich (G-rich) oligodeoxynucleotides (ODNs) can inhibit the adhesion of certain tumor cells. However, no data exist on how inclusion of the CpG motif in the G-rich sequence influences tumor cell adhesion and subsequent tumorigenesis. In this study, in vitro and in vivo assays were used to evaluate how a panel of ODN-containing contiguous guanosines and the CpG motif influenced adhesion of B16 melanoma cells. The results showed that a self-designed ODN, named BW001, containing the polyG motif and a full phosphorothioate modification backbone could inhibit B16 melanoma cell adhesion on a culture plate or on a plate coated with various substances. In vivo data revealed that B16 melanoma cells co-administered with BW001 and intraperitoneally injected into mice formed fewer tumor colonies in peritoneal cavities. This effect was related to the polyG motif and the full phosphorothioate modification backbone and enhanced by the existence of the CpG motif. Additional in vivo data showed that survival of tumor-bearing mice in the BW001 group was significantly prolonged, subcutaneous melanoma developed much more slowly, and lung dissemination colonies formed much less often than in mice inoculated with B16 melanoma cells only. The effect was CpG motif-dependent. These results suggest that BW001 may exert an integrated antitumor effect.