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首页> 外文期刊>Neoplasia: an international journal for oncology research >The Differential Effects of Anti-Diabetic Thiazolidinedione on Prostate Cancer Progression Are Linked to the TR4 Nuclear Receptor Expression Status
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The Differential Effects of Anti-Diabetic Thiazolidinedione on Prostate Cancer Progression Are Linked to the TR4 Nuclear Receptor Expression Status

机译：抗糖尿病噻唑烷二酮对前列腺癌进展的差异效应与TR4核受体表达状况相关联

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The insulin sensitizers, thiazolidinediones (TZDs), have been used as anti-diabetic drugs since the discovery of their ability to alter insulin resistance through transactivation of peroxisome proliferator-activated receptors (PPARs). However, their side effects in hepatitis, cardiovascular diseases, and bladder cancer resulted in some selling restrictions in the USA and Europe. Here, we found that the potential impact of TZDs on the prostate cancer (PCa) progression might be linked to the TR4 nuclear receptor expression. Clinical surveys found that 9% of PCa patients had one allele TR4 deletion in their tumors. TZD increased cell growth and invasion in PCa cells when TR4 was knocked down. In contrast, TZD decreased PCa progression in PCa cells with wild type TR4. Mechanism dissection found that the Harvey Rat Sarcoma (HRAS) oncogene increased on TZD treatment of the TR4 knocked-down CWR22Rv1 and C4-2 cells, and interruption with HRAS inhibitor resulted in reversal of TZD-induced PCa progression. Together, these results suggest that TZD treatment may promote PCa progression depending on the TR4 expression status that may be clinically relevant since extra caution may be needed for those diabetic PCa patients receiving TZD treatment who have one allele TR4 deletion.
机译：胰岛素敏化剂，噻唑烷二酮（TZDS）已被用作抗糖尿病药物，因为发现它们通过过氧化物体增殖物激活的受体（PPAR）的转移来改变胰岛素抗性的能力。然而，它们在肝炎，心血管疾病和膀胱癌中的副作用导致了美国和欧洲的一些销售限制。在这里，我们发现TZDS对前列腺癌（PCA）进展的潜在影响可能与TR4核受体表达相关联。临床调查发现，9％的PCA患者在其肿瘤中有一个等位基因TR4缺失。当TR4被敲下来时，TZD增加了PCA细胞中的细胞生长和侵袭。相比之下，具有野生型TR4的PCA细胞中的TZD降低了PCA进展。机制解剖发现，哈维大鼠肉瘤（HRAS）癌基因在TZD敲除CWR22RV1和C4-2细胞的TZD处理上增加，以及HRAS抑制剂的中断导致TZD诱导的PCA进展逆转。这些结果表明，TZD治疗可以根据TR4表达状态促进PCA进展，这可能是临床相关的，因为接受具有一个等位基因TR4缺失的TZD治疗的糖尿病PCA患者可能需要额外的警告。

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