Interferon-alpha prevents selection of doxorubicin-resistant undifferentiated-androgen-insensitive metastatic human prostate cancer cells.
BACKGROUND
We determined whether treatment of metastatic prostate cancer cells with doxorubicin (DOX) and interferon-alpha (IFN-alpha) prevented the emergence of highly undifferentiated tumor cells.


METHODS
The state of cell differentiation was determined by analysis of prostate-specific antigen (PSA), E-cadherin, keratin, and vimentin.


RESULTS
Human prostate cancer LNCaP-LN3 cells growing in culture as multicell spheroids expressed higher levels of E-cadherin and E-cadherin-associated beta-catenin than LNCaP-LN3 cells growing as monolayers. Treatment of cells with DOX downregulated PSA, E-cadherin, and keratin, and upregulated expression of vimentin and vascular endothelial growth factor (VEGF) mRNA. While treatment of cells with IFN-alpha did not alter gene expression, the addition of IFN-alpha to cultures treated with DOX produced synergistic toxicity and abrogated the changes in gene expression observed in cells treated with DOX alone.


CONCLUSIONS
Treatment with IFN-alpha and DOX should be further explored as a therapeutic strategy for androgen-insensitive prostate cancer.
Kuniyasu
H
H
Department of Oncological Pathology, Cancer Center, Nara Medical University, Kashihara, Japan.
Yasui
W
W
Pettaway
C A
CA
Yano
S
S
Oue
N
N
Tahara
E
E
Fidler
I J
IJ
D000728:Androgens / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015820:Cadherins / Q000032:analysis / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects*; D002471:Cell Transformation, Neoplastic; D004317:Doxorubicin / Q000494:pharmacology*; D004347:Drug Interactions; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D007633:Keratins / Q000032:analysis / Q000096:biosynthesis; D008297:Male; D017430:Prostate-Specific Antigen / Q000032:analysis / Q000096:biosynthesis; D011471:Prostatic Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D014746:Vimentin / Q000032:analysis / Q000096:biosynthesis
D000728:Androgens; D000970:Antineoplastic Agents; D015820:Cadherins; D016898:Interferon-alpha; D014746:Vimentin; D007633:Keratins; D004317:Doxorubicin; D017430:Prostate-Specific Antigen