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Interferon‐alpha prevents selection of doxorubicin‐resistant undifferentiated‐androgen‐insensitive metastatic human prostate cancer cells
Author(s) -
Kuniyasu Hiroki,
Yasui Wataru,
Pettaway Curtis A.,
Yano Seiji,
Oue Naohide,
Tahara Eiichi,
Fidler Isaiah J.
Publication year - 2001
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.1114
Subject(s) - prostate cancer , cancer research , lncap , vimentin , prostate , medicine , doxorubicin , pca3 , cancer , biology , chemotherapy , immunohistochemistry
BACKGROUND We determined whether treatment of metastatic prostate cancer cells with doxorubicin (DOX) and interferon‐alpha (IFN‐α) 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 β‐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‐α did not alter gene expression, the addition of IFN‐α 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‐α and DOX should be further explored as a therapeutic strategy for androgen‐insensitive prostate cancer. Prostate 49:19–29, 2001. © 2001 Wiley‐Liss, Inc.