- 作者：Megan D. Indermaur ; Yin Xiong ; Siddharth G. Kamath ; Todd Boren ; Ardeshir Hakam ; Robert M. Wenham ; Sachin M. Apte ; Johnathan M. Lancaster
- 关键词：doxorubicin ; endometrial cancer ; microarray gene analysis ; Src pathway ; targeted therapy
- 刊名：American Journal of Obstetrics and Gynecology
- 出版年：2010
- 出版时间：August 2010
- 年：2010
- 卷：203
- 期：2
- 页码：158.e1-158.e40
- 全文大小：1964 K
Objective
We aimed to utilize genome-wide expression analysis to identify molecular pathways that may contribute to endometrial cancer resistance to doxorubicin (DOX) and that also represent therapeutic targets to increase DOX sensitivity.Study Design
Ten endometrial cancer cell lines were subjected to gene expression analysis. Sensitivity of each endometrial cell line to DOX was quantified by dimethylthiazoldiphenyltetrazoliumbromide cell proliferation assay. Pearson's correlation test was used to identify genes associated with response to DOX. Genes associated with DOX responsiveness were analyzed, and identified pathways were subjected to targeted inhibition.
Results
Pearson's correlation analysis identified 2871 genes associated with DOX resistance (P < .05), which included members of the Src pathway. Targeted inhibition of the Src pathway increased DOX sensitivity in RL 95-2 (P < .0001), HEC 1B (P < .001), MEF 296 (P < .05), and MEF 280 (P = .14) cell lines.
Conclusion
Genomic analysis can identify therapeutic targets such as the Src pathway that may influence endometrial cancer DOX sensitivity.