目的：观察人卵巢癌顺铂（cisplatin，CDDP）敏感细胞株OVCAR-3和耐药细胞株OVCAR-3/CDDP生物学行为的差异，并探讨其可能的机制。方法：取对数生长期的OVCAR-3和OVCAR-3/CDDP细胞，软琼脂克隆形成实验检测细胞的增殖能力；Transwell小室、失巢凋亡实验和裸鼠皮下移植瘤实验分别检测细胞体外和体内的侵袭、迁移能力；免疫组织化学实验检测移植瘤组织中MMP-2和MMP-9的表达。结果：与OVCAR-3细胞比较，OVCAR-3/CDDP细胞克隆形成能力显著增加 \[（0.66±0.09）% vs（0.31±0.07）%，P<0.05\]。Transwell小室实验发现，OVCAR-3/CDDP细胞较OVCAR-3细胞侵袭和迁移能力均明显增强\[（233.1±8.5）vs（167.4±5.9），P<0.01；（143.6±9.1）vs（95.8±6.2），P<0.01\]； OVCAR-3/CDDP细胞较OVCAR-3细胞更易聚集，细胞凋亡指数下降\[（7.78±1.32）% vs（15.41±1.26）%，P<0.01\]。OVCAR-3/CDDP细胞移植瘤组织中MMP-2、MMP-9的表达高于OVCAR-3细胞。结论：顺铂耐药OVCAR-3/CDDP细胞的增殖、抗失巢凋亡、侵袭和迁移能力显著增强，其机制可能与MMP-2和MMP-9表达升高有关。

Objective:To investigate the differences in biological behavior between cisplatin-sensitive (OVCAR-3 cells) and cisplatin-resistant human ovarian cancer cells (OVCAR-3/CDDP cells), and to explore the possible mechanisms. Methods: OVCAR-3 and OVCAR-3/CDDP cells in logarithmic phase were collected, their proliferation were assessed by soft agar colony formation assay, their in vitro and in vivo invasion and migration abilities were measured by Transwell chamber assay, anoikis assay and subcutaneous transplanted-tumor formation assay in nude mice, and the expressions of MMP-2 and MMP-9 in transplanted tumor tissues were examined by immunohistochemical assay. Results: Colony formation rate of OVCAR-3/CDDP cells was significantly increased compared with OVCAR-3 cells (\[0.66%±009%\] vs \[0.31%±0.07%\], P<0.05). Compared with OVCAR-3 cells, OVCAR-3/CDDP cells had significantly higher migration capability (\[233.1±8.5\] vs \[167.4±5.9\], P<0.01) and invasive capability (\[143.6±9.1\] vs \[95.8±6.2\], P<0.01). OVCAR-3/CDDP cells tended to aggregate and their apoptosis index was decreased compared with that OVCAR-3 cells (\[7.78±1.32\]% vs \[15.41±1.26\]%, P<0.01). The expressions of MMP-2 and MMP-9 in transplanted tumor tissues of OVCAR-3/CDDP cell group were up-regulated compared with those of OVCAR-3 cell group (P<0.05). Conclusion: The proliferation, anti-anoikis, invasion and migration abilities of cisplatin-resistant OVCAR-3/CDDP cells are greatly increased, which might be related with the up-regulation of MMP-2 and MMP-9.

全军医学科学技术研究“十一五”面上课题（No. MB2151）