Reversal Effect of A Novel N-sugar Substituted Thalidomide Analogue on Multidrug Resistant Human Nasopharyngeal Carcinoma Cells
- VernacularTitle:N糖基取代的沙利度胺新衍生物对人鼻咽癌细胞耐药逆转作用研究
- Author:
Wenyuan YI
;
Bo XU
;
Min LI
;
Zhongjun LI
;
Jingrong CUI
- Publication Type:Journal Article
- Keywords:
thalidomide, multidrug resistance, TAX, KB cell, P-glycoprotein
- From:
Progress in Biochemistry and Biophysics
2006;0(01):-
- CountryChina
- Language:Chinese
-
Abstract:
One major problem to successful treatment of cancer is the development of resistance by tumor cells to multiple chemotherapeutic drugs, a phenomenon named multidrug resistance (MDR). Searching for the novel chemotherapeutical agents is one of the important strategies for overcoming MDR. By using a cytotoxicity assay, flow cytometry analysis, Western-blotting and RT-PCR, a drug (Taxol, TAX) resistant human nasopharyngeal carcinoma KB cell line (KB/TAX) was established by addition of the drug to the cell cultures gradually, then a novel N-sugar substituted thalidomide analogue (STA-35) was investigated for its reversal effect on MDR of KB/TAX cells and possible mechanism. The results showed that KB/TAX cells were resistant to several chemotherapeutical agents, and the relative resistance to TAX was 73.1. Compared with parental KB cells, the function and protein expression of P-glycoprotein (P-gp), as well as mdr1 gene in the KB/TAX cells were remarkable reduced. Moreover, both KB and KB/TAX cells were sensitive to STA-35, the relative resistance to TAX on KB/TAX cells was decreased by the addition of STA-35. Furthermore, STA-35 (5 ～20 ?mol/L)was capable to reduced the activity of P-gp by increasing the accumulation of rhodamine 123, decreasing P-gp expression in KB/TAX cells in a dose dependent manner , but had no effect on the mdr1 gene expression. These results suggest a potential action of STA-35 as MDR reversing agent, and one of the possible mechanisms could be the suppression of P-gp function and protein expression.
