Yu Shaonan, Chen Yan, Li Xuefeng, Gao Zhongli, Liu Guifeng
Department of Radiology, China-Japan Union Hospital of Jilin University, 130033 Changchun, China.
Department of Endocrinology, Second Hospital of Jilin University, 130041 Changchun, China.
Biosci Rep. 2017 Jun 27;37(3). doi: 10.1042/BSR20170122. Print 2017 Jun 30.
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 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 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.
趋化因子（C-X-C基序）受体4（CXCR4）已被报道为人类乳腺癌中预后不良的生物标志物，并被认为是乳腺癌治疗中一个有前景的治疗靶点。本研究旨在研究壳聚糖将小干扰RNA（siRNA）递送至乳腺癌细胞的效率，进而考察壳聚糖纳米颗粒递送的siRNA对乳腺癌细胞CXCR4表达及化学敏感性的调控作用。我们的结果表明，壳聚糖可将siRNA包裹成直径为80-110 nm、ζ电位为20-50 mV的纳米颗粒。壳聚糖纳米颗粒将siRNA高效递送至乳腺癌MCF-7细胞，显著降低了CXCR4在mRNA和蛋白水平的表达。此外，壳聚糖纳米颗粒递送的siRNA导致CXCR4表达降低，这与乳腺癌细胞对顺铂的敏感性增加有关。与对照siRNA组相比，CXCR4 siRNA组MCF-7细胞的生长受到抑制且凋亡增加。综上所述，我们的结果显示了壳聚糖纳米颗粒递送靶向CXCR4的siRNA在乳腺癌治疗中的潜力。
