Effects of hormone deprivation and 2-methoxyestradiol combination therapy on hormone-dependent prostate cancer in vivo.
2-Methoxyestradiol (2-ME) has potent antiproliferative effects on cancer cells. Its utility alone or in combination with other therapies for treating prostate cancer, however, has not been fully explored. Androgen-dependent and independent human prostate cancer cells were examined in vivo for their response to combination therapy. Efficacy was assessed by terminal deoxynucleotide transferase-mediated dUTP nick-end labeling assay and measuring microvessel density (MVD) in excised tumors. Animals harboring hormone-dependent tumors treated with 2-ME alone, androgen deprivation therapy alone, or the combination of the two had a 3.1-fold, 5.3-fold, and 10.1-fold increase in apoptosis, respectively. For hormone-independent tumors, treatment with 2-ME resulted in a 2.43-fold increase in apoptosis and a 73% decrease in MVD. 2-ME was most effective against hormone-dependent tumors in vivo and combination therapy resulted in a significant increase in efficacy compared to no treatment controls and trended toward greater efficacy than either 2-ME or androgen deprivation alone. Combination therapy should be investigated further as an additional therapeutic option for early prostate cancer.
Sato
Fuminori
F
Center for Molecular Imaging Research and NFCR-Center for Molecular Analysis and Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
Fukuhara
Hiroshi
H
Basilion
James P
JP
D000077584:2-Methoxyestradiol; D000728:Androgens / Q000502:physiology*; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004958:Estradiol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D051379:Mice; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy; D009919:Orchiectomy; D017430:Prostate-Specific Antigen / Q000032:analysis; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000628:therapy; D011944:Receptors, Androgen / Q000032:analysis; D023041:Xenograft Model Antitumor Assays
D000728:Androgens; D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D011944:Receptors, Androgen; D004958:Estradiol; D000077584:2-Methoxyestradiol; D017430:Prostate-Specific Antigen