Wang Jin, Chan Judy Yuet-Wa, Fong Chi-Chun, Tzang Chi-Hung, Fung Kwok-Pui, Yang Mengsu
Department of Biology and Chemistry, and Applied Research Centre for Genomics Technology, City University of Hong Kong, Hong Kong, China.
Liver Int. 2009 Oct;29(9):1338-47. doi: 10.1111/j.1478-3231.2009.02081.x. Epub 2009 Jul 16.
BACKGROUND/AIMS: Hepatoma is either intrinsically resistant to chemotherapy or response to it but later develop resistance. The aim of this study was to clarify the relationship of treatment with doxorubicin (Dox) in hepatoma HepG2 cells and drug resistance developed by Dox.
We have analysed the bioactivities and gene expression profiles of multidrug resistant (MDR) HepG2/DR cell line and its parental HepG2 cell, which were exposure to Dox.
We confirmed that Dox-induced apoptosis of HepG2 cells in a time-dependent manner; cDNA microarray and hierarchical cluster analysis demonstrate that the features of the transcriptional programme of the later response to Dox in HepG2 cells and MDR HepG2/DR cells have a common character, which is upregulation of stress response, cytoskeleton, ubiquitin-proteasome pathway and repressed G-protein signal transduction system; differentially expressed genes in MDR HepG2/DR such as drug transporters and tumour-associated antigens were verified at the levels of mRNA by semiquantitative reverse transcriptase-polymerase chain reaction.
These results reveal novel co-ordinated changes that occurred in resistant HepG2 cells to survive from cell apoptosis elicited by Dox treatment.
背景/目的：肝癌要么对化疗具有内在抗性，要么对化疗有反应但随后会产生抗性。本研究的目的是阐明肝癌HepG2细胞中阿霉素（Dox）治疗与Dox诱导的耐药性之间的关系。
我们分析了多药耐药（MDR）HepG2/DR细胞系及其亲代HepG2细胞在暴露于Dox后的生物活性和基因表达谱。
我们证实Dox以时间依赖性方式诱导HepG2细胞凋亡；cDNA微阵列和层次聚类分析表明，HepG2细胞和MDR HepG2/DR细胞对Dox后期反应的转录程序特征具有共同特点，即应激反应、细胞骨架、泛素-蛋白酶体途径上调，G蛋白信号转导系统受抑制；通过半定量逆转录-聚合酶链反应在mRNA水平验证了MDR HepG2/DR中差异表达的基因，如药物转运体和肿瘤相关抗原。
这些结果揭示了耐药HepG2细胞为从Dox治疗引起的细胞凋亡中存活而发生的新的协同变化。
