Versican is a potential therapeutic target in docetaxel-resistant prostate cancer
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https://doi.org/10.18632/oncoscience.136
Naoko Arichi1, Yozo Mitsui1,2, Miho Hiraki1, Sigenobu Nakamura1, Takeo Hiraoka1, Masahiro Sumura1, Hiroshi Hirata2, Yuichiro Tanaka2, Rajvir Dahiya2, Hiroaki Yasumoto1, Hiroaki Shiina1
1 Departments of Urology, Shimane University Faculty of Medicine, Izumo, Japan
2 Department of Urology, San Francisco Veterans Affairs Medical Center and University of California San Francisco, San Francisco, California
Correspondence:
Naoko Arichi, email:
Keywords: versican, taxane resistance, castration resistant prostate cancer, thalidomide chemotherapy
Received: November 6, 2014 Accepted: February 27, 2015 Published: March 2, 2015
Abstract
In the current study, we investigated a combination of docetaxel and thalidomide (DT therapy) in castration-resistant prostate cancer (CRPC) patients. We identified marker genes that predict the effect of DT therapy. Using an androgen-insensitive PC3 cell line, we established a docetaxel-resistant PC-3 cell line (DR-PC3). In DR-PC3 cells, DT therapy stronger inhibited proliferation/viability than docetaxel alone. Based on gene ontology analysis, we found versican as a selective gene. This result with the findings of cDNA microarray and validated by quantitative RT-PCR. In addition, the effect of DT therapy on cell viability was the same as the effect of docetaxel plus versican siRNA. In other words, silencing of versican can substitute for thalidomide. In the clinical setting, versican expression in prostate biopsy samples (before DT therapy) correlated with PSA reduction after DT therapy (p<0.05). Thus targeting versican is a potential therapeutic strategy in docetaxel-resistant prostate cancer.
