MDR1/P-gp and VEGF Synergistically Enhance the Invasion of Hep-2 Cells with Multidrug Resistance Induced by Taxol

• Published in: Annals of surgical oncology Vol. 16; no. 5; pp. 1421 - 1428
• Main Authors: Li, Li, Jiang, Alice C., Dong, Pin, Wang, Haibo, Xu, Wei, Xu, Chengzhi
• Format: Journal Article
• Language: English
• Published: New York Springer-Verlag 01-05-2009; Springer Nature B.V
• Subjects: Antineoplastic Agents, Phytogenic - pharmacology; ATP Binding Cassette Transporter, Sub-Family B; ATP-Binding Cassette, Sub-Family B, Member 1 - biosynthesis; Cell Line, Tumor; Drug Resistance, Multiple - drug effects; Drug Resistance, Neoplasm - drug effects; Humans; Laryngeal Neoplasms - drug therapy; Laryngeal Neoplasms - metabolism; Medicine; Medicine & Public Health; Neoplasm Invasiveness; Oncology; Original Article-Translational Research and Biomarkers; Paclitaxel - pharmacology; Surgery; Surgical Oncology; Vascular Endothelial Growth Factor Receptor-2 - biosynthesis; Vascular Endothelial Growth Factor; Invasive Ability; Taxol; MDR1 Expression; Express Vascular Endothelial Growth Factor Receptor
• ISSN: 1068-9265; 1534-4681
• DOI: 10.1245/s10434-009-0395-7

Background
Tumor invasion/metastasis and multidrug resistance (MDR) are the main causes of treatment failure and high mortality in all kinds of cancer patients. The relationship between the two factors is still unclear. The aim of this study is to investigate the association between MDR and invasion, especially the role of multidrug resistance 1/P-glycoprotein (MDR1/P-gp) and vascular endothelial growth factor (VEGF) during the invasion.
Methods
Multidrug resistance 1 (MDR1) and VEGF receptor 2 (VEGFR-2) were detected with real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) and Western blotting at the levels of messenger RNA (mRNA) and protein, respectively. RNA interference was applied to inhibit the expression of MDR1. The invasive assays were performed with the CHEMICON cell invasion assay kit.
Results
The MDR cell line induced by Taxol (Hep-2T cell) was more invasive than its parent cell line (Hep-2 cell), which was at least in part mediated through the overexpressed MDR1/P-pg. MDR1-targeted RNA interference could effectively inhibit the expression of MDR1 and obviously decrease the invasive ability. Synergistic enhancing effects existed between MDR1/P-gp and VEGF on the invasion of Hep-2T cells. The expression of VEGFR-2 was elevated in Hep-2T cells. SU1498 could significantly decrease the invasion of Hep-2T cells. MDR1-targeted RNA interference and SU1498 had synergistic decreasing effect on the invasion of Hep-2T cells.
Conclusions
MDR1/P-pg may be a risk predictor for the invasion of laryngeal cancer. MDR1 knock down and VEGFR-2 inhibitor may be two promising treatment regiments for advanced laryngeal carcinoma patients with MDR and invasion/metastasis.