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.

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.