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Published on: June 13, 2014
Preparing PAMAM-NK4 nano complexes and examining their in vitro growth suppression effects in breast cancer
Minfeng Liu1, Zhaoze Guo1, Jiangqin Liu1
1Breast Center, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Background:
This study sought to examine the suppression of the NK4 (which is a fragment that originates from the trypsin digestion of the hepatocyte growth factor) gene as mediated by new nano material polyamidoamine (PAMAM) dendrimers in the growth of breast cancer cells MDA-MB-231 and MCF-7, and the therapeutic effects in a nude mice model of transplanted tumor cell MDA-MB-231.
Methods:
We built PAMAM-NK4 nano particles and detected the in vitro transfection rate. Nano complexes and blank plasmid PAMAM dendrimers were transfected to MDA-MB-231 and MCF-7 cells, respectively. The western-blotting method, MTT experiment method, and bead method were used to detect the effects of the nano complexes on NK4 protein expression, cell proliferation, and cell apoptosis. The nude mice model of transplanted tumor cell MDA-MB-231 comprised 40 nude female mice who were subject to injections. The mice were randomly divided into four groups, comprising 10 mice per group. The control, blank plasmid and treatment groups were subcutaneously injected with 0.2 mL of 0.9% NaCl (Sodium chloride) solution, 0.2 mL of plasmid solution (including 100 µg PAMAM pcDNA3.1(-) blank plasmid nano complexes) and 0.2 mL of plasmid solution (including PAMAM-NK4 100 µg) beside the tumor inoculation spot, respectively. The positive control group was intraperitoneally injected with 0.2 mL of doxorubicin solution, including 100 µg doxorubicin. Western blotting was used to detect the NK4 protein expression of the transplanted tumor tissues of the various groups.
Results:
NK4 protein was successfully expressed in MDA-MB-231 and MCF-7 cells transfected with PAMAM-NK4 nano particles, and cell proliferation was suppressed and cell apoptosis was induced. The tumor volumes and masses of the treatment and positive control groups were obviously smaller than those of the control group. The differences were statistically significant (P<0.05). The treatment group had an obviously higher mean value of NK4 protein expression than the control group. The differences were statistically significant (P<0.05).
Conclusions:
PAMAM-NK4 nano complexes suppress the growth of the breast cancer cells MDA-MB-231 and MCF-7, and had a treatment effect on this tumor nude mice model of breast cancer cells.
Insights
New polyamidoamine (PAMAM) dendrimers carrying NK4 effectively suppressed breast cancer cell growth and induced apoptosis. This NK4-PAMAM nanoparticle demonstrated therapeutic effects in a nude mice model, reducing tumor volume and mass.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Breast cancer remains a significant global health challenge, necessitating novel therapeutic strategies.
- Hepatocyte growth factor (HGF) and its fragment NK4 play roles in tumor progression.
- Polyamidoamine (PAMAM) dendrimers offer potential as drug delivery vehicles for cancer therapy.
Purpose of the Study:
- To investigate the efficacy of PAMAM-NK4 nanoparticles in suppressing breast cancer cell growth (MDA-MB-231 and MCF-7).
- To evaluate the therapeutic potential of PAMAM-NK4 in a preclinical nude mouse model of breast cancer.
Main Methods:
- Construction and in vitro transfection of PAMAM-NK4 nanoparticles.
- Assessment of NK4 protein expression, cell proliferation (MTT assay), and apoptosis (bead method).
- Evaluation of therapeutic effects in a MDA-MB-231 tumor xenograft nude mouse model, comparing PAMAM-NK4 treatment with control and doxorubicin.
Main Results:
- Successful transfection and expression of NK4 protein in breast cancer cells using PAMAM-NK4 nanoparticles.
- Significant suppression of cell proliferation and induction of apoptosis in vitro.
- Demonstrated reduction in tumor volume and mass in the treatment group compared to controls, with significant NK4 protein expression.
Conclusions:
- PAMAM-NK4 nanoparticles effectively inhibit the proliferation of MDA-MB-231 and MCF-7 breast cancer cells.
- PAMAM-NK4 nanoparticles exhibit therapeutic efficacy in a preclinical model of breast cancer, warranting further investigation.
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