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Secreted Frizzled Related Protein 1 Modulates Taxane Resistance of Human Lung Adenocarcinoma Jin Ren, Rui Wang, Haizhu Song, Guichun Huang, and Longbang Chen Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China Taxanes, such as docetaxel and taxol, have been used as firstline chemotherapies in advanced lung adenocarcinoma (LAD), but limited responses to chemotherapy remain a major impediment in the clinic. Treatment with 5-azacytidine increases the sen- sitivity of SPC-A1/DTX cell line to taxanes. The results of DNA methylation microarray and cDNA array analysis indicate that DNA methylation contributes to the downregulation of secreted frizzled related protein 1 (SFRP1) in SPC-A1/DTX cells. Overexpression of SFRP1 reverses the chemoresistance of taxane-resistant LAD cell lines and enhances the in vivo sensitivity of taxane-resistant LAD cells to taxanes. Meanwhile, short hairpin RNA (shRNA)-mediated SFRP1 knockdown decreases the sensitivity of parental LAD cell lines to taxanes. Furthermore, FH535, a reversible Wnt signaling inhibitor, enhances the sensitivity of taxane-resistant LAD cells to taxanes. The level of SFRP1 in tumors of nonresponding patients is significantly lower than that in tumors of responders. Taken to- gether, our results provide the direct evidence that SFRP1 is a clinically important determinant of taxanes resistance in human LAD cells, suggesting that SFRP1 might be a novel therapeutic target for the treatment of taxane-resistant LAD patients. Online address: doi: 10.2119/molmed.2013.00149 INTRODUCTION Aberrant DNA methylation of the CpG tal SPC-A1 cell line. SFRP1, a 35-kDa se- Lung cancer is the leading cause of islands plays an important role in the de- creted glycoprotein, is well described as cancer-related death around th