Interferon-alpha prevents selection of doxorubicin-resistant undifferentiated-androgen-insensitive metastatic human prostate cancer cells
Interferon-alpha prevents selection of doxorubicin-resistant undifferentiated-androgen-insensitive metastatic human prostate cancer cells
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DOI：
10.1002/pros.1114
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发表时间：
2001-09-15
期刊：
影响因子：
2.8
通讯作者：
Fidler, IJ
中科院分区：
文献类型：
--
作者：
Kuniyasu, H;Yasui, W;Fidler, IJ
背景我们确定了用阿霉素（DOX）和干扰素-α（IFN-α）治疗转移性前列腺癌细胞是否能防止高度未分化肿瘤细胞的出现。通过分析前列腺特异性抗原（PSA）、E-钙粘蛋白、角蛋白和波形蛋白来确定细胞的分化状态。在培养物中生长为多细胞球体的人前列腺癌LNCaP-LN 3细胞比生长为单层的LNCaP-LN 3细胞表达更高水平的E-钙粘蛋白和E-钙粘蛋白相关的β-连环蛋白。用DOX处理细胞下调PSA、E-钙粘蛋白和角蛋白，上调波形蛋白和血管内皮生长因子（VEGF）mRNA的表达。虽然用IFN-α处理细胞并不改变基因表达，但向用DOX处理的培养物中加入IFN-α产生协同毒性，并消除了在单独用DOX处理的细胞中观察到的基因表达变化。用IFN-α和DOX治疗应该进一步探索作为雄激素不敏感的前列腺癌的治疗策略，前列腺49：19-29，2001。(C)2001 Wiley-Liss，Inc.
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, Prostate 49: 19-29, 2001. (C) 2001 Wiley-Liss, Inc.