Adeno-associated virus type 2-mediated gene transfer of a short hairpin-RNA targeting human IGFBP-2 suppresses the proliferation and invasion of MDA-MB-468 cells
| Autor: | Nan Zheng, Chao Gao, Chen Wang, Ru‑Song Zhang |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research Genetic Vectors Transplantation Heterologous Down-Regulation Mice Nude tumor xenografts Breast Neoplasms Recombinant virus Biochemistry Metastasis Small hairpin RNA Mice 03 medical and health sciences breast cancer 0302 clinical medicine Cell Movement Cell Line Tumor Genetics medicine Animals Humans RNA Small Interfering invasion ability Adeno-Associated Virus Type 2 Molecular Biology Cell Proliferation Mice Inbred BALB C Oncogene MDA-MB-468 Chemistry Articles Transfection Dependovirus medicine.disease Insulin-Like Growth Factor Binding Protein 2 tumor growth 030104 developmental biology Oncology Cell culture AAV2 030220 oncology & carcinogenesis Cancer research Matrix Metalloproteinase 2 Molecular Medicine Female RNA Interference MDA-MB-468 cells |
| Zdroj: | Molecular Medicine Reports |
| ISSN: | 1791-3004 1791-2997 |
| Popis: | Adeno-associated virus 2 (AAV2) is prepotent in the biological treatment of breast tumor because of its low pathogenicity and immunogenicity. Our previous study demonstrated that insulin-like growth factor-binding protein 2 (IGFBP-2) was highly expressed in patients with breast metastasis. In the present study, the effects of recombinant AAV2 on the growth and metastasis of breast cancer cells were determined in vitro, and in vivo. rAAV2-ZsGreen-shRNA-scramble and rAAV2-ZsGreen-shRNA-hIGFBP-2 were used to transfect MDA-MB-468, and MCF-10A cells respectively, and observed that these virus could not penetrate the normal human breast epithelia MCF-10A cell line. To investigate the effect of the recombinant virus on chemotherapeutics, paclitaxel was added to MDA-MB-468 cells and it was demonstrated that rAAV2-ZsGreen-shRNA-hIGFBP-2-infected MDA-MB-468 cells were highly chemosensitive to paclitaxel compared with rAAV2-ZsGreen-shRNA-scramble-injected cells. In addition, it was demonstrated that the invasive ability of rAAV2-ZsGreen-shRNA-hIGFBP-2-infected MDA-MB-468 cells was highly impaired compared with the rAAV2-ZsGreen-shRNA-scramble group. In the nude mice xenografts, the rAAV2-ZsGreen-shRNA-hIGFBP-2 injection inhibited tumor growth and Ki-67 expression was significantly downregulated compared with the scramble group. Following IGFBP-2 knockdown using rAAV2-ZsGreen-shRNA-hIGFBP-2, matrix metalloproteinase-2 expression was significantly reduced in tumor tissues compared with that in rAAV2-ZsGreen-shRNA-scramble treated tumor tissues. These findings have provided a direction for the application of novel AAV2-based therapeutics for treating aggressive triple-negative breast cancer types. |
| Databáze: | OpenAIRE |
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