Dopamine receptor antagonist thioridazine inhibits tumor growth in a murine breast cancer model.
Dopamine receptor antagonist thioridazine inhibits tumor growth in a murine breast cancer model.
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多巴胺受体拮抗剂硫利达嗪抑制小鼠乳腺癌模型中的肿瘤生长。
DOI：
10.3892/mmr.2015.3967
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发表时间：
2015-09
影响因子：
3.4
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Yin T;He S;Shen G;Ye T;Guo F;Wang Y
神经心理学因素已被证明影响肿瘤进展和治疗反应。本研究探讨多巴胺受体拮抗剂硫利达嗪对小鼠乳腺癌的影响。使用鼠乳腺癌模型评估硫利达嗪的抗肿瘤功效。采用流式细胞术（FCM）和MTT法分别检测细胞凋亡和增殖情况。进行蛋白质印迹分析以评估用硫利达嗪处理后肿瘤细胞中的Akt、磷酸化（p）-Akt、信号转导子和转录激活子（STAT）3、p-STAT 3和p-p65。在肿瘤切片中评估Ki 67指数和末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）阳性凋亡细胞的数量。硫利达嗪在体外以剂量和时间依赖性的方式减少肿瘤生长，抑制肿瘤细胞增殖并诱导凋亡。硫利达嗪还被发现在体内显著抑制肿瘤增殖并诱导肿瘤细胞凋亡，如较低的Ki 67指数和TUNEL阳性细胞的增加所示。此外，观察到硫利达嗪可抑制活化B细胞途径的经典核因子κ-轻链增强子的活化，并通过重塑肿瘤基质发挥抗肿瘤作用，以及抑制肿瘤微环境中的血管生成。总之，发现硫利达嗪显著抑制乳腺肿瘤生长，并且可以在临床环境中重新评估和研究硫利达嗪用于癌症治疗的潜力。
Neuropsychological factors have been shown to influence tumor progression and therapeutic response. The present study investigated the effect of the dopamine receptor antagonist thioridazine on murine breast cancer. The anti-tumor efficacy of thioridazine was assessed using a murine breast cancer model. Cell apoptosis and proliferation were analyzed in vitro using flow cytometry (FCM) and the MTT assay, respectively. Western blot analysis was performed to assess Akt, phosphorylated (p)-Akt, signal transducer and activator of transcription (STAT) 3, p-STAT3 and p-p65 in tumor cells following treatment with thioridazine. The Ki67 index and the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic cells were assessed in the tumor sections. Thioridazine was found to reduce tumor growth, inhibit tumor cell proliferation and induce apoptosis in a dose- and time-dependent manner in vitro. Thioridazine was also found to markedly inhibit tumor proliferation and induce tumor cell apoptosis in vivo as shown by the lower Ki67 index and increase in TUNEL-positive cells. In addition, thioridazine was observed to inhibit the activation of the canonical nuclear factor κ-light-chain-enhancer of activated B cells pathway and exert anti-tumor effects by remodeling the tumor stroma, as well as inhibit angiogenesis in the tumor microenvironment. In conclusion, thioridazine was found to significantly inhibit breast tumor growth and the potential for thioridazine to be used in cancer therapy may be re-evaluated and investigated in clinical settings.