Ovarian cancer cells with different drug-resistant abilities: A comparison of migration and invasion capability
10.3724/SP.J.1008.2011.00117
- Author:
Dan WANG
1
Author Information
1. Department of Obstetrics and Gynecology
- Publication Type:Journal Article
- Keywords:
Cisplatin;
Matrix metalloproteinases;
Neoplasm drug resistance;
Neoplasm invasiveness;
Neoplasm metastasis;
Ovarian neoplasms
- From:
Academic Journal of Second Military Medical University
2011;32(2):117-122
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To observe the relationship between drug-resistance and invasive metastatic behaviors in ovarian cancer cells, and to discuss the related mechanism. Methods: Human 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). Results: OVCAR-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/G 1 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). Conclusion: Development 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.