Effect of low-molecular-weight heparin combined with paclitaxel on the invasiveness and migration of nasopharyngeal carcinoma cells in vitro.
- Author:
Pei ZHANG
1
;
Surong ZHAO
;
Lele SONG
;
Longjian PU
;
Zhiwen JIANG
;
Hao LIU
;
Chenchen JIANG
Author Information
- Publication Type:Journal Article
- MeSH: Carcinoma; Cell Line, Tumor; Cell Movement; drug effects; Cell Proliferation; drug effects; Glucuronidase; metabolism; Heparin Lyase; metabolism; Heparin, Low-Molecular-Weight; administration & dosage; pharmacology; Humans; Matrix Metalloproteinase 9; metabolism; Nasopharyngeal Neoplasms; pathology; Paclitaxel; administration & dosage; pharmacology; Tissue Inhibitor of Metalloproteinase-1; metabolism
- From: Journal of Southern Medical University 2012;32(11):1529-1535
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the effect of low-molecular-weight heparin (LMWH) combined with paclitaxel (PTX) on the invasiveness and migration of nasopharyngeal carcinoma cells and explore the molecular mechanisms.
METHODSMTT assay was used to detect the growth inhibition induced by LMWH and PTX in CNE1 and CNE2 cells. Wound healing assay and Transwell migration assay were employed to assess the effects of the drugs on the cell migration, and Transwell invasion assay was used to evaluate the cell invasiveness. The cellular expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) were analyzed by Western blotting. ELISA was used to determine the expression of heparanase (HPA) in the culture medium of the cells.
RESULTSMTT assay showed an obvious suppression of CNE1 and CNE2 cell proliferation in response to LMWH and PTX treatments. Treatment with 200 U·ml LMWH combined with 0.1 µmol·L PTX for 24 h resulted in the inhibition rates of migration of 66.70% and 70.53% in CNE1 and CNE2 cells, respectively significantly higher than the rates in cells with PTX treatment alone. The combined treatment with LMWH and PTX for 24 h also caused a significantly higher inhibition rate of cell invasion than LMWH and PTX alone. LMWH enhanced the down-regulation of MMP-9 and HPA induced by PTX.
CONCLUSIONLMWH can enhance the inhibitory effect of PTX on the migration and invasion of nasopharyngeal carcinoma cells, the mechanism of which may involve the down-regulation of MMP-9 and HPA expressions.