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.
The relation between the alignment of chromosomes in the aged oocyte and its capacities of fertilization and development of oocytes was examined. More embryos in the condition of insemination at 12 and 16 h after human chorionic gonadotropin (hCG) however grew into two and more cell stages than those in the insemination of 20, 24 and 28 h. Some embryos in the group of insemination at 12, 16 and 20 h after hCG injection had grown into the blastocyst stage. The embryos inseminated 24 h after hCG and later had shown no further development. Twelve hours after hCG injection, 67% of oocytes have chromosomes on a straight line (A), and 29% have chromosomes scattered in one group (B). Three percent of oocytes have them separated toward both spindle ends (C) and 2% of oocytes have no chromosomes (D). At 16 h after hCG, the alignments of chromosomes are almost the same as that of 12 h after hCG injection. At 20 h after hCG, the most common alignment of chromosomes was scattered in a small group. The alignment of chromosomes of most oocytes was splitting at 24 and 28 h after hCG injection. Thus the oocytes with the chromosome alignment of A or B can be fertilized and developed into the blastocyst stage. The alignment of A and B lasts only about 8 h after ovulation, and the time was extremly restricted for oocytes to develop normally.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.