Jia Yijun, Weng Ziyi, Wang Chuanying, Zhu Mingjie, Lu Yunshu, Ding Longlong, Wang Yongkun, Cheng Xianhua, Lin Qing, Wu Kejin
Department of General Surgery, XinHua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.
Department of General Surgery, Shanghai International Medical Center, Shanghai 201318, P.R. China.
Oncol Lett. 2017 Jan;13(1):206-214. doi: 10.3892/ol.2016.5402. Epub 2016 Nov 21.
Hypoxia is a major cause of treatment resistance in breast cancer. Single-walled carbon nanotubes (SWCNTs) exhibit unique properties that make them promising candidates for breast cancer treatment. In the present study, a new functionalized single-walled carbon nanotube carrying oxygen was synthesized; it was determined whether this material could increase chemosensitivity and radiosensitivity of human breast cancer cell lines, and the underlying mechanisms were investigated. MDA-MB-231 cells growing in folic acid (FA) free medium, MDA-MB-231 cells growing in medium containing FA and ZR-75-1 cells were treated with chemotherapy drugs or radiotherapy with or without tombarthite-modified-FA-chitosan (R-O-FA-CHI)-SWCNTs under hypoxic conditions, and the cell viability was determined by water-soluble tetrazolium salts-1 assay. The cell surviving fractions were determined by colony forming assay. Cell apoptosis induction was monitored by flow cytometry. Expression of B-cell lymphoma 2 (Bcl-2), survivin, hypoxia-inducible factor 1-α (HIF-1α), multidrug resistance-associated protein 1 (MRP-1), P-glycoprotein (P-gp), RAD51 and Ku80 was monitored by western blotting. The novel synthesized R-O-FA-CHI-SWCNTs were able to significantly enhance the chemosensitivity and radiosensitivity of human breast cancer cell lines and the material exhibited its expected function by downregulating the expression of Bcl-2, survivin, HIF-1α, P-gp, MRP-1, RAD51 and Ku80.
缺氧是乳腺癌治疗耐药的主要原因。单壁碳纳米管(SWCNTs)具有独特的性能,使其成为乳腺癌治疗的有希望的候选材料。在本研究中,合成了一种新的载氧功能化单壁碳纳米管;确定了该材料是否能增加人乳腺癌细胞系的化学敏感性和放射敏感性,并研究了其潜在机制。在缺氧条件下,用化疗药物或放疗处理在无叶酸(FA)培养基中生长的MDA-MB-231细胞、在含FA培养基中生长的MDA-MB-231细胞和ZR-75-1细胞,同时添加或不添加铈改性-FA-壳聚糖(R-O-FA-CHI)-SWCNTs,通过水溶性四唑盐-1检测法测定细胞活力。通过集落形成试验确定细胞存活分数。通过流式细胞术监测细胞凋亡诱导情况。通过蛋白质印迹法监测B细胞淋巴瘤2(Bcl-2)、生存素、缺氧诱导因子1-α(HIF-1α)、多药耐药相关蛋白1(MRP-1)、P-糖蛋白(P-gp)、RAD51和Ku80的表达。新合成的R-O-FA-CHI-SWCNTs能够显著增强人乳腺癌细胞系的化学敏感性和放射敏感性,并且该材料通过下调Bcl-2、生存素、HIF-1α、P-gp、MRP-1、RAD51和Ku80的表达发挥了预期功能。