Tumor-targeting, systemically delivered antisense HER-2 chemosensitizes human breast cancer xenografts irrespective of HER-2 levels.

摘要: BACKGROUND: The failure to respond chemotherapy is a major obstacle in the successful treatment of breast cancer. We have previously shown that anti-HER-2 antisense oligonucleotide (AS HER-2 ODN) was able sensitize cancer cells various chemotherapeutic agents vitro irrespective their status, indicating use AS ODN therapy for not limited tumors overexpressing protein. One main drawbacks clinical setting lack an efficient, tumor-targeting, systemic delivery method. developed tumor-specific, ligand-targeting, cationic liposome system designed gene In this study we employ ligand-liposome strategy enhance Her-2 cells, including those do overexpress HER-2, and vivo. MATERIALS AND METHODS: A complex includes folate as targeting ligand optimized more efficient vitro, significantly, with tumor-specific Human cell line MDA-MB-435, which does used compare degree chemosensitization taxanes delivered via folate-liposome versuscommercial Lipofectin. MDA-MB-435 xenograft were also evaluate anti-tumor effect combination systemically folate-liposome-AS docetaxel (Taxotere). RESULTS: significantly increases response tumor lines conventional compared unliganded commercially available reagent, vivo, has prolonged stability blood increased uptake tumors. More intravenously administered ligand-liposome-AS resulted marked inhibition growth aggressive model even after ended. CONCLUSIONS: Although there are other reports liposomal ODNs, first report vivo efficacy against human using tumor-targeting therapy. Moreover, circulation observed obtained without need continuous intravenous infusion. integral component within network pathways can affect many different types where may be contributing factor, such ovarian, esophageal, GI malignancies colon pancreatic cancers. Therefore, effectiveness potential expand usefulness efficacious form