Susceptibility of PTEN-positive metastatic tumors to small interfering RNA targeting the mammalian target of rapamycin
| Autor: | Masafumi Yokota, Tomohiro Asai, Hiroyuki Koide, Takehisa Dewa, Hidenori Ando, Mamoru Nango, Noriyuki Maeda, Norihito Yonenaga, Hiroki Kato, Naoto Oku |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Male
Small interfering RNA 1 2-Dipalmitoylphosphatidylcholine Angiogenesis Melanoma Experimental Biomedical Engineering Pharmaceutical Science Medicine (miscellaneous) Bioengineering macromolecular substances Biology Polyethylene Glycols Mice PEG ratio Animals PTEN General Materials Science Neoplasm Metastasis Phosphorylation RNA Small Interfering Melanoma Protein kinase B PI3K/AKT/mTOR pathway Cell Proliferation Tube formation Neovascularization Pathologic Phosphatidylethanolamines TOR Serine-Threonine Kinases PTEN Phosphohydrolase technology industry and agriculture Ethylenediamines Molecular biology Mice Inbred C57BL Liposomes Cancer research biology.protein Molecular Medicine |
| Zdroj: | Nanomedicine: Nanotechnology, Biology and Medicine. 11:185-194 |
| ISSN: | 1549-9634 |
| DOI: | 10.1016/j.nano.2014.09.003 |
| Popis: | PTEN-positive tumors are not susceptible to the treatment with rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR). Here, we determined the susceptibility of PTEN-positive cells to small interfering RNA for mTOR (si-mTOR) by using a novel liposomal delivery system. We prepared dicetyl phosphate-tetraethylenepentamine-based polycation liposomes (TEPA-PCL) decorated with polyethylene glycol (PEG) grafting Ala-Pro-Arg-Pro-Gly (APRPG), a VRGFR-1-targeting peptide. APRPG-PEG-decorated TEPA-PCL carrying si-mTOR (APRPG-TEPA-PCL/si-mTOR) had an antiproliferative effect against B16F10 murine melanoma cells (PTEN-positive) and significantly inhibited both the proliferation and tube formation of mouse 2H-11 endothelial-like cells (PTEN-positive). APRPG-TEPA-PCL/si-mTOR treatment did not induce Akt phosphorylation (Ser473) in either B16F10 or 2H-11 cells although there was strong phosphorylation of Akt in response to rapamycin treatment. Intravenous injection of APRPG-TEPA-PCL/si-mTOR significantly suppressed the tumor growth compared with rapamycin treatment in mice bearing B16F10 melanoma. These findings suggest that APRPG-TEPA-PCL/si-mTOR is useful for the treatment of PTEN-positive tumors. |
| Databáze: | OpenAIRE |
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