Abstract
Chemokine (C-X-C motif) receptor 4 (CXCR4) has been reported as a poor prognostic biomarker in human breast cancers, and has been suggested as a promising therapeutic target of breast cancer treatment. The present study aims to investigate the delivery efficiency of siRNA by chitosan into breast cancer cells, and then to examine the regulatory role by chitosan nanoparticle-delivered siRNA on CXCR4 expression and on the chemosensitivity of breast cancer cells. Our results demonstrated that the siRNA could be capsuled by chitosan into nanoparticles with a diameter of 80–110 nm, and with a zeta potential of 20–50 mV. The chitosan nanoparticle delivered siRNA efficiently into breast cancer MCF-7 cells significantly reduced the expression of CXCR4 in both mRNA and protein levels. Moreover, the reduced CXCR4 by chitosan nanoparticle-delivered siRNA was associated with increased sensitivity of breast cancer cells to cisplatin. Reduced growth and increased apoptosis of MCF-7 cells were observed in the CXCR4 siRNA group than in the control siRNA group. Taken together, our results present the treatment potential of chitosan nanoparticle-delivered siRNA targeting CXCR4 in breast cancers.
Highlights
Breast cancer is the leading cause of cancer death in females worldwide
The chemokine receptor 4 (CXCR4) expression in protein level of treated A human breast adenocarcinoma cell line (MCF-7) cells was detected by western blottin (WB)
We investigated the delivery efficiency of siRNA by chitosan into breast cancer cells, and examined the regulatory role by chitosan nanoparticle-delivered siRNA on CXCR4 expression and on the chemosensitivity of breast cancer cells
Summary
1 of 8 women in western countries is affected by breast cancer, and 5% of which is caused by mutations in breast cancer associated gene 1 (BRCA1) and breast cancer associated gene 2 (BRCA2) [1,2]. Most of patients receive combined chemotherapy when diagnosed, but approximately 30% of these patients die of metastatic disease within 5 years [3]. Cisplatin is a conventional drug for breast cancer and for other solid tumors. It is a crosslink-inducing DNA-damaging agent that may induce cell death by damaging cytoplasmic proteins and by inducing apoptosis at the execution phase level [4,5]. Cisplatin causes cytotoxicity to normal tissues, and cancer cells acquire resistance and reduce the drug’s toxicity [7]. Previous studies have indicated that the development of drug resistance is correlated with the tumor microenvironment, and chemokines seem to play key roles in tumor progression and metastasis [8,9]
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