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  • 王丹1△,陈超2△,惠宁1*.不同化疗耐药性卵巢癌细胞侵袭转移特性的比较[J].第二军医大学学报,2011,32(2):117-122    [点击复制]
  • WANG Dan1△,CHEN Chao2△,HUI Ning1*.Ovarian cancer cells with different drug-resistant abilities: a comparison of migration and invasion capability[J].Acad J Sec Mil Med Univ,2011,32(2):117-122   [点击复制]
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不同化疗耐药性卵巢癌细胞侵袭转移特性的比较
王丹1△,陈超2△,惠宁1*
0
(1.第二军医大学长海医院妇产科,上海 200433;2.第二军医大学长海医院中心实验室,上海 200433)
摘要:
[摘要]目的观察不同化疗耐药性卵巢癌细胞的侵袭转移特性,并探讨其可能机制。方法体外建立卵巢癌不同梯度顺铂(DDP)耐药细胞系模型(OVCAR-3/DDP-1、OVCAR-3/DDP-2、OVCAR-3/DDP-3);MTT法、流式细胞仪、Transwell小室观察亲本细胞和耐药细胞的增殖、细胞周期分布、细胞侵袭和迁移等生物学特性的变化;ELISA法测定细胞培养上清液中基质金属蛋白酶-2(MMP-2)、组织金属蛋白酶抑制因子-2(TIMP-2)、基质金属蛋白酶-9(MMP-9)、组织金属蛋白酶抑制因子-1(TIMP-1)的浓度。结果成功建立不同梯度顺铂耐药细胞系模型,OVCAR-3/DDP-1、DDP-2、DDP-3细胞的耐药指数依次为3.87、8.39、13.42。耐药细胞均较亲本细胞增殖缓慢,G0/G1期细胞比例增加,S期细胞比例减少,其中OVCAR-3/DDP-2、DDP-3与亲本细胞比较差异有统计学意义(P<0.05)。与亲本细胞相比,耐药细胞伴随其耐药性的增加,侵袭转移能力逐渐增强,其中OVCAR-3/DDP-2、DDP-3与亲本细胞相比差异有统计学意义(P<0.05)。细胞上清液中MMP-2/TIMP-2、MMP-9/TIMP-1的比值随顺铂耐药性的增加而逐渐上升,耐药细胞与亲本细胞相比差异均有统计学意义(P<0.05)。结论对顺铂耐药性的产生和增加可促进卵巢癌细胞的侵袭和转移,可能部分与耐药细胞MMP-2/TIMP-2、MMP-9/TIMP-1比值上调有关。
关键词:  卵巢肿瘤  顺铂  肿瘤抗药性  肿瘤侵袭  肿瘤转移  基质金属蛋白酶
DOI:10.3724/SP.J.1008.2011.0117
投稿时间:2010-12-10修订日期:2011-01-25
基金项目:
Ovarian cancer cells with different drug-resistant abilities: a comparison of migration and invasion capability
WANG Dan1△,CHEN Chao2△,HUI Ning1*
(1. Department of Obstetrics and Gynecology, Changhai Hospital, Second Military Medical University,Shanghai 200433,China;;2. Central Laboratory, Changhai Hospital, Second Military Medical University, Shanghai 200433,China)
Abstract:
[Abstract]ObjectiveTo observe the relationship between drug-resistance and invasive metastatic behaviors in ovarian cancer cells, and to discuss the related mechanism.MethodsHuman ovarian cancer cell lines with different levels of cisplatin-resistance, namely, OVCAR-3/DDP-1, -2, and -3, were established in vitro. The cell proliferation, cell cycle, and cell migration and invasion were assessed by MTT assay, flow cytometry, and Transwell migratory and invasive assays. The protein levels of MMP-2, TIMP-2, MMP-9, and TIMP-1 in the culture supernatants were determined by enzyme-linked immunosorbent assay (ELISA). ResultsOVCAR-3/DDP-1, -2, -3 cell lines with stable resistance to cisplatin were successfully established, with the resistance indices being 3.87, 8.39, and 13.42, respectively. Compared with the parent cells, OVCAR-3/DDP-1, -2, and -3 exhibited a lower growth rate; the ratios of cells in G0/G1 phase were increased and those in S phase were decreased, with significant difference found between OVCAR-3/DDP-2 and -3 cells with OVCAR-3 cells(P<0.05). With the enhancement of drug resistance, the invasion and migration capabilities of OVCAR-3/DDP-1, -2, and -3 cells were increased, with significant difference found between OVCAR-3/DDP-2 and -3 cells with the OVCAR-3 cells(P<0.05). The ratios of MMP-2/TIMP-2 and MMP-9/TIMP-1 were increased in the cisplatin-resistant cells,with significant difference found between the OVCAR-3/DDP-1, -2, and -3 cells with the OVCAR-3 cells(P<0.05). ConclusionDevelopment and enhancement of cisplatin resistance can promote the invasive and metastatic abilities of OVCAR-3 cells, which is partially related to up-regulated ratios of MMP-2/TIMP-2 and MMP-9/TIMP-1 in the resistant cells.
Key words:  ovarian neoplasms  cisplatin  neoplasm drug resistance  neoplasm invasiveness  neoplasm metastasis  matrix metalloproteinases