Castrate resistant prostate cancer (CRPC) is a disease that is resistant to both hormone therapy and
chemotherapy. At present, no curative therapy for CRPC has been established. Therefore, it is necessary to determine a
novel molecular target for the development of therapeutic agents. We previously reported that AlkB homolog 3
(ALKBH3) is highly expressed in prostate cancer but not in benign prostatic hyperplasia or in normal prostate epithelium
and that the expression levels of ALKBH3 protein are significantly correlated with the hormone-independent state of
prostate cancer. Moreover, ALKBH3 regulates the invasion of prostate cancer cells via the regulation of matrix
metalloproteinase 9. Here, we show that ALKBH3 gene silencing markedly induces apoptosis in hormone-independent
prostate cancer cell line DU145 but not in the normal prostate epithelial cell line PNT2. Moreover, the in vivo
tumorigenicity of DU145 cells was significantly inhibited by the administration of ALKBH3 siRNA. Furthermore, the
anchorage-independent growth of DU145 cells was inhibited by ALKBH3 knockdown and promoted by ALKBH3
overexpression, significantly. ALKBH3 shRNA-expressing prostate cancer cells formed significantly smaller tumors than
those of control shRNA transfectants in an in vivo xenograft model. These findings suggest that ALKBH3 is a promising
target molecule for the development of CRPC therapeutic agents.
Keywords: Akt, AlkB, ALKBH, anchorage-independent, castrate resistant prostate cancer, demethylase, AlkB homolog 3, androgen receptor, Castrate resistant prostate cancer, inositol polyphosphate 4-phosphatase type II, magnetic resonance imaging, mammalian target of rapamycin, prostate cancer antigen-1.
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