Mechanism of Drug Resistance Identified in Human Lung Adenocarcinoma Cell Line SPC-A1 Selected for Resistance to Docetaxel

Objective: To investigate the mechanism of resistance to docetaxel in human lung cancer. Methods: Human lung carcinoma SPC-A1/Docetaxel cells were derived from parental SPC-A1 cells by continuous exposure to increasing concentration of docetaxel. The drug sensitivity was measured by MTT assay in vit...

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Veröffentlicht in:Chinese journal of cancer research 2009-09, Vol.21 (3), p.207-216
Hauptverfasser: Sun, Hai, Chen, Long-bang
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description Objective: To investigate the mechanism of resistance to docetaxel in human lung cancer. Methods: Human lung carcinoma SPC-A1/Docetaxel cells were derived from parental SPC-A1 cells by continuous exposure to increasing concentration of docetaxel. The drug sensitivity was measured by MTT assay in vitro. The cDNA microarray identified a set of differentially expressed genes, and some genes were confirmed by RT-PCR. P-glycoprotein level was measured by flow cytometry analysis. Results: The results of drug sensitivity measured by MTT assay showed that SPC-A1/Docetaxel cells were 13.2-fold resistant to docetaxel and cross-resistant at varying levels to other drugs. The cDNA microarray results identified a set of differentially expressed genes, which showed 428 genes that were up-regulated and 506 genes that were down-regulated in SPC-A1/Docetaxel ceils, and some genes were confirmed by RT-PCR. Flow cytometry analysis suggests expression of P-glycoprotein (P-gp) was more abundant in SPC-A1/Docetaxel cells than in the parental cells and docetaxel selection reduces the apoptotic response. Conclusion: The results suggest that docetaxel selection led to changes in gene expression that contribute to the multidrug resistance phenotype.
doi_str_mv 10.1007/s11670-009-0207-4
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Methods: Human lung carcinoma SPC-A1/Docetaxel cells were derived from parental SPC-A1 cells by continuous exposure to increasing concentration of docetaxel. The drug sensitivity was measured by MTT assay in vitro. The cDNA microarray identified a set of differentially expressed genes, and some genes were confirmed by RT-PCR. P-glycoprotein level was measured by flow cytometry analysis. Results: The results of drug sensitivity measured by MTT assay showed that SPC-A1/Docetaxel cells were 13.2-fold resistant to docetaxel and cross-resistant at varying levels to other drugs. The cDNA microarray results identified a set of differentially expressed genes, which showed 428 genes that were up-regulated and 506 genes that were down-regulated in SPC-A1/Docetaxel ceils, and some genes were confirmed by RT-PCR. Flow cytometry analysis suggests expression of P-glycoprotein (P-gp) was more abundant in SPC-A1/Docetaxel cells than in the parental cells and docetaxel selection reduces the apoptotic response. Conclusion: The results suggest that docetaxel selection led to changes in gene expression that contribute to the multidrug resistance phenotype.</description><identifier>ISSN: 1000-9604</identifier><identifier>EISSN: 1993-0631</identifier><identifier>DOI: 10.1007/s11670-009-0207-4</identifier><language>eng</language><publisher>Heidelberg: Chinese Anti-Cancer Association</publisher><subject>Anti-Cancer Pharmacology ; cDNA微阵列 ; Medicine ; Medicine &amp; Public Health ; SPC ; 多西紫杉醇 ; 差异表达基因 ; 流式细胞仪分析 ; 耐药性 ; 耐药机制 ; 肺癌细胞</subject><ispartof>Chinese journal of cancer research, 2009-09, Vol.21 (3), p.207-216</ispartof><rights>Chinese Anti-Cancer Association and Springer-Verlag GmbH 2009</rights><rights>Copyright © Wanfang Data Co. Ltd. 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Cancer Res</addtitle><addtitle>Chinese Journal of Cancer Research</addtitle><description>Objective: To investigate the mechanism of resistance to docetaxel in human lung cancer. Methods: Human lung carcinoma SPC-A1/Docetaxel cells were derived from parental SPC-A1 cells by continuous exposure to increasing concentration of docetaxel. The drug sensitivity was measured by MTT assay in vitro. The cDNA microarray identified a set of differentially expressed genes, and some genes were confirmed by RT-PCR. P-glycoprotein level was measured by flow cytometry analysis. Results: The results of drug sensitivity measured by MTT assay showed that SPC-A1/Docetaxel cells were 13.2-fold resistant to docetaxel and cross-resistant at varying levels to other drugs. The cDNA microarray results identified a set of differentially expressed genes, which showed 428 genes that were up-regulated and 506 genes that were down-regulated in SPC-A1/Docetaxel ceils, and some genes were confirmed by RT-PCR. Flow cytometry analysis suggests expression of P-glycoprotein (P-gp) was more abundant in SPC-A1/Docetaxel cells than in the parental cells and docetaxel selection reduces the apoptotic response. 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J. Cancer Res</stitle><addtitle>Chinese Journal of Cancer Research</addtitle><date>2009-09-01</date><risdate>2009</risdate><volume>21</volume><issue>3</issue><spage>207</spage><epage>216</epage><pages>207-216</pages><issn>1000-9604</issn><eissn>1993-0631</eissn><abstract>Objective: To investigate the mechanism of resistance to docetaxel in human lung cancer. Methods: Human lung carcinoma SPC-A1/Docetaxel cells were derived from parental SPC-A1 cells by continuous exposure to increasing concentration of docetaxel. The drug sensitivity was measured by MTT assay in vitro. The cDNA microarray identified a set of differentially expressed genes, and some genes were confirmed by RT-PCR. P-glycoprotein level was measured by flow cytometry analysis. Results: The results of drug sensitivity measured by MTT assay showed that SPC-A1/Docetaxel cells were 13.2-fold resistant to docetaxel and cross-resistant at varying levels to other drugs. The cDNA microarray results identified a set of differentially expressed genes, which showed 428 genes that were up-regulated and 506 genes that were down-regulated in SPC-A1/Docetaxel ceils, and some genes were confirmed by RT-PCR. Flow cytometry analysis suggests expression of P-glycoprotein (P-gp) was more abundant in SPC-A1/Docetaxel cells than in the parental cells and docetaxel selection reduces the apoptotic response. Conclusion: The results suggest that docetaxel selection led to changes in gene expression that contribute to the multidrug resistance phenotype.</abstract><cop>Heidelberg</cop><pub>Chinese Anti-Cancer Association</pub><doi>10.1007/s11670-009-0207-4</doi><tpages>10</tpages></addata></record>
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source EZB-FREE-00999 freely available EZB journals
subjects Anti-Cancer Pharmacology
cDNA微阵列
Medicine
Medicine & Public Health
SPC
多西紫杉醇
差异表达基因
流式细胞仪分析
耐药性
耐药机制
肺癌细胞
title Mechanism of Drug Resistance Identified in Human Lung Adenocarcinoma Cell Line SPC-A1 Selected for Resistance to Docetaxel
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