Su Shan, Sun Xueqin, Zhang Qinghua, Zhang Zhe, Chen Ju
Department of Gynecology, the Central Hospital of Zibo.
Department of Ultrasound, the Central Hospital of Zibo.
Cell Struct Funct. 2019;44(1):21-28. doi: 10.1247/csf.18029.
Ovarian cancer (OC) is one of prevalent tumors and this study aimed to explore CCL20's effects on doxorubicin resistance of OC and related mechanisms. Doxorubicin-resistant SKOV3 DR cells were established from SKOV3 cells via 6-month continuous exposure to gradient concentrations of doxorubicin. Quantitative PCR and Western blot assay showed that SKOV3 DR cells had higher level of CCL20 than SKOV3 cells, and doxorubicin upregulated CCL20 expression in SKOV3 cells. MTT and cell count assay found that CCL20 overexpression plasmid enhanced doxorubicin resistance of SKOV3 and OVCA433 cells compared to empty vector, as shown by the increase in cell viability. In contrast, CCL20 shRNA enhanced doxorubicin sensitivity of SKOV3 DR cells compared to control. CCL20 overexpression plasmid promoted NF-kB activation and positively regulated ABCB1 expression. Besides, ABCB1 overexpression plasmid enhanced the viability of SKOV3 and OVCA433 cells compared to empty vector under treatment with the same concentration of doxorubicin, whereas ABCB1 shRNA inhibited doxorubicin resistance of SKOV3 DR cells compared to control. In conclusion, CCL20 enhanced doxorubicin resistance of OC cells by regulating ABCB1 expression.Key words: CCL20, ovarian cancer, doxorubicin resistance, tumor-promoting, ABCB1.
卵巢癌（OC）是常见肿瘤之一，本研究旨在探讨CCL20对OC多柔比星耐药性的影响及相关机制。通过将SKOV3细胞连续6个月暴露于梯度浓度的多柔比星，建立了多柔比星耐药的SKOV3 DR细胞。定量PCR和蛋白质印迹分析表明，SKOV3 DR细胞中CCL20水平高于SKOV3细胞，且多柔比星上调了SKOV3细胞中CCL20的表达。MTT和细胞计数分析发现，与空载体相比，CCL20过表达质粒增强了SKOV3和OVCA433细胞对多柔比星的耐药性，细胞活力增加表明了这一点。相反，与对照相比，CCL20 shRNA增强了SKOV3 DR细胞对多柔比星的敏感性。CCL20过表达质粒促进NF-κB激活并正向调节ABCB1表达。此外，在相同浓度多柔比星处理下，与空载体相比，ABCB1过表达质粒增强了SKOV3和OVCA433细胞的活力，而与对照相比ABCB1 shRNA抑制了SKOV3 DR细胞对多柔比星的耐药性。总之，CCL20通过调节ABCB1表达增强了OC细胞对多柔比星的耐药性。关键词：CCL20；卵巢癌；多柔比星耐药性；肿瘤促进；ABCB1
