Inhibitory effect of PAMAM-NK4 nanocomposite on the growth of breast cancer xenografts in nude mice
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Abstract:
Objective:To explore the inhibitory effect of polyamidoamine dendrimer (PAMAM)-mediated NK4 gene on the growth of breast cancer cell lines MDA-MB-231 and MCF-7, and its therapeutic effect on MDA-MB-231 cell transplantation tumor in nude mouse model. Methods: PAMAM-NK4 nanoparticles and blank plamids were prepared and respectively transfected into MDA-MB-231 and MCF-7 cells as the experiment group (PAMAM-NK4 group) and the control group (PAMAM group). MTT, Western blotting and flow cytometry assays were used to examine effect of the PAMAM-NK4 transfection on proliferation of the cells, expression of NK4 protein and apoptosis of the cells, respectively. Forty female nude mice were subcutaneous injected with human breast cancer MDA-MB-231 cell to establish nude mouse model with the xenograft tumor. The mice were randomly divided into 4 groups with 10 mice in each. Mice of the blank control group were subcutaneously injected with 0.2 ml of 0.9% NaCl surrounding the xenograft tumor, those of the blank plasmid group with 0.2 ml of plasmid solution containing 100 μg PAMAM-LacZ, those of the PAMAM-NK4 group with 0.2 ml of plasmid solution containing 100 μg PAMAM-NK4 and those of the positive control group with 0.2 ml of solution containing 100 μg adriamycin, respectively. All of the nude mice were continuously injected for 7 d and then sacrificed on 30th day. The xenograft tumors were removed completely to measure their weights and sizes. Expressions of the NK4 protein in the xenograft tissues were detected by Western blotting assay. Results: The transfection of PAMAM-NK4 nanocomposites, could result in stable expression of the NK4 protein, and inhibition of the cell proliferation and promotion of the cell apoptosis. The nude mouse models with human breast carcinoma xenogragts were successfully constructed. The volumes and weights of the carcinoma xenografts in the PAMAM-NK4 and the positive control groups were significantly smaller than those in the blank control group (P<0.05) with a fairly good safety. The expression of NK4 protein in the PAMAM-NK4 group significantly increased, comparing with that in the blank control group (P<0.05). Conclution: PAMAM-NK4 nanocomposites could inhibit growth of the breast cancer MDA-MB-231 and MCF-7 cells, and have therapeutic effect on the human breast carcinoma xenografts in nude mouse model.
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Project supported by the Science and Technology Planning Programe of Guangdong Province (No. 2013B010404023)