ABSTRACT
PURPOSE: The specific targeting of interleukin-4 receptor α (IL4Rα) receptor offers a promising therapeutic approach for inhibition of tumor cell progression in breast cancer patients. In the current study, the in vitro efficacy of superparamagnetic iron oxide nanoparticles conjugated with anti-IL4Rα blocking antibodies (SPION-IL4Rα) via polyethylene glycol polymers was evaluated in 4T1 breast cancer cells. MATERIALS AND METHODS: Cell viability, reactive oxygen species generation, and apoptosis frequency were assessed in vitro in 4T1 cancer cell lines following exposure to SPION-IL4Rα alone or combined with doxorubicin. In addition, immunofluorescence assessments and fluorimetrywere performed to confirm the specific targeting and interaction of the developed nanocarriers with IL4Rα receptors in breast cancer cells. RESULTS: Blocking of IL4Rα receptors caused a significant decrease in cell viability and induced apoptosis in 4T1 cells. In addition, combined treatment with SPION-IL4Rα+doxorubicin caused significant increases in cell death, apoptosis, and oxidative stress compared to either SPION-IL4Rα or doxorubicin alone, indicating the enhanced therapeutic efficacy of this combination. The decrease in fluorescence intensity upon immunofluorescence and fluorimetry assays combined with increased viability and decreased apoptosis following the blocking of IL4Rα receptors confirmed the successful binding of the synthesized nanocarriers to the target sites on murine 4T1 breast cancerous cells. CONCLUSION: These results suggest that SPION-IL4Rα nanocarriers might be used for successfulreduction of tumor growth and inhibition of progression of metastasis in vivo.
Subject(s)
Humans , Antibodies, Blocking , Apoptosis , Biomarkers , Breast Neoplasms , Breast , Cell Death , Cell Line , Cell Proliferation , Cell Survival , Doxorubicin , Drug Delivery Systems , Fluorescence , Fluorescent Antibody Technique , Fluorometry , In Vitro Techniques , Interleukin-4 , Iron , Nanoparticles , Neoplasm Metastasis , Oxidative Stress , Polyethylene Glycols , Polyethylene , Polymers , Reactive Oxygen SpeciesABSTRACT
Two common polymorphisms in cytrochronme P450; family 1, subfamily A, polypeptide 1 [CYP1A1]; has been implicated as a risk factor of prostate cancer, but individual studies have been inconclusive or controversial. We reviewed studies on CYP1A1 polymorphisms in patients with prostate cancer. The strategy searching in the PubMed was based on combinations of prostate cancer, CYP1A1, CYP1A1 gene polymorohism, and genetic susceptibility. The last search update was May 2008. The retrieved articles and their bibliographies of were evaluated and reviewed independently by 2 experts. We shortlisted 19 studies, of which 14 on sporadic prostate cancer were analyzed. The random effects odds ratio was 1.350 [95% confidence interval, 1.110 to 1.641; P=.003] for T/C polymorphism and 1.085 [95% confidence interval, 0.863 to 1.364; P=.49] for A/G polymorphism. The A/G polymorphism was not associated with increased risk of prostate cancer. However, the T/C polymorphism showed conflicting results in different studies, while overall, this polymorphism showed significant effects on susceptibility to prostate cancer. There was no significant between study heterogeneity for both polymorphisms with respect to distributed of alleles. This meta-analysis suggests that while the CYP1A1 T/C polymorphism is likely to considerably increase the risk of sporadic prostate cancer on a wide population basis, the A/G polymorphism may not influence this risk. However, the association of polymorphisms may be significant with respect to smoking history, diet habits, ethnicity, and race