Establishment of human lung adenocarcinoma multidrug resistance cell lines induced by paclitaxel and the mRNA expressions of DNA pol?,mdr1,mrp1,GST-?,lrp,and topo Ⅱ genes
- VernacularTitle:紫杉醇诱导人肺腺癌多药耐药细胞系的建立及DNA pol?、mdr1、mrp1、GST-?l、rp和topo Ⅱ基因的表达
- Author:
Zhiju WANG
;
Hongkun FAN
;
Min LI
;
Guoqiang ZHAO
;
Ziming DONG
- Publication Type:Journal Article
- Keywords:
human;
lung adenocarcinoma;
multidrug resistance;
paclitaxel;
DNA pol?
- From:
Journal of Xi'an Jiaotong University(Medical Sciences)
1982;0(04):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective To establish human lung adenocarcinoma multidrug resistance cell lines in vitro,observe their biological characteristics,and investigate the mRNA expressions of DNA pol?,mdr 1,mrp1,GST-?,lrp and topo Ⅱ genes.Methods Paclitaxel-resistant cell lines(A549/TXL20) were established in vitro by exposure to stepwise increased concentrations of the drug in a cell culture medium.Biological morphology and cell cycles were analyzed by morphometry and flow cytometry.The chemoresistance indexes of cells were measured by methyl tetrazolium assay.Evaluation of growth and in vitro drug sensitivity were performed.RT-PCR was employed to analyze the mRNA expressions of the DNA pol?,mdr 1,mrp1,GST-?,lrp,and topo Ⅱ genes.Results ① Compared with parent cells,the resistant sublines had a lower confluent density.They were smaller and mixed with giant cells in different sizes and with different numbers of nucleoli,and the growth property of A549/TXL20 did not change significantly compared with A549 cell lines.② The resistant cells,A549/TXL20,were 19.3 times more resistant to paclitaxel and 67.4 times more resistant to cisplatin than the parent cells,and also demonstrated cross-resistance to mitomycin,vinblastine,and 5-fluouracil(5-FU). ③ Compared with the A549 celllines,an unreasonably higher level of drug resistance and lower drug concentration was detected in A549/TXL20 cells after exposure to the drug in the culture medium.④ The mRNA expression level of DNA pol?,mdr1,GST-?,mrp1 andlrp genes in A549/TXL20 cells was significantly higher than that in A549 cell lines(P
