硫利达嗪在子宫内膜癌中的重要应用。
The important application of thioridazine in the endometrial cancer.
作者信息
Meng Qiong, Sun Xiao, Wang Jing, Wang Yudong, Wang Lihua
机构信息
Department of Anesthesiology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai, China.
Laboratory for Gynecologic Oncology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai, China.
出版信息
Am J Transl Res. 2016 Jun 15;8(6):2767-75. eCollection 2016.
BACKGROUND
Endometrial cancer (ECa) is one of the serious healthy burden for female worldwide. The treatments of ECa focus on the application of endocrine therapy and aberrant signaling proteins expression recently years. Medroxyprogesterone acrtate (MPA) plays crucial role in the endocrine therapy for ECa patients. However, the outcomes are still not ideal in the advanced stage tumor, especially in the progesterone-resistant ECa. Thioridazine (THIO) is an anti-psychotic agent, which has been reported to suppress the development of several human cancers. In this study, we aimed at to explore the clinical significant of THIO in the treatment of ECa.
METHODS
Two ECa cell lines (ISK and KLE) were enrolled in this study, and were grouped into fore groups based on the treatment with different agents. Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay was used to analyze the viability of ECa cell lines. The apoptosis of ECa cells was examined by using the flow cytometer. To investigate the expression of important proteins, we applied the quantitative real-time RT-PCR (qRT-PCR) method and western blot analysis.
RESULTS
The viability of ECa cells was downregulated, and the apoptosis of ECa cells was upregulated after treating with the THIO plus MPA. The expression of progesterone receptor B (PRB) and dopamine receptor D2 (DRD2) were increased, and epidermal growth factor receptor (EGFR) and p-AKT were decreased in the THIO+MPA group. All these results suggested that the THIO could promote MPA to inhibit the growth of cells in ECa, especially in the progesterone-resistant ECa.
CONCLUSION
Taken together, all the data in the present study suggested that the THIO plus MPA might act as the suppressor of tumor growth in ECa by inhibiting the PI3K/AKT signal transduction pathway, which was mediated by PRB, DRD2 and EGFR.
背景
子宫内膜癌（ECa）是全球女性面临的严重健康负担之一。近年来，ECa的治疗主要集中在内分泌治疗和异常信号蛋白表达方面。醋酸甲羟孕酮（MPA）在ECa患者的内分泌治疗中起着关键作用。然而，晚期肿瘤的治疗效果仍不理想，尤其是对孕激素抵抗的ECa。硫利达嗪（THIO）是一种抗精神病药物，据报道可抑制多种人类癌症的发展。在本研究中，我们旨在探讨THIO在ECa治疗中的临床意义。
方法
本研究纳入了两种ECa细胞系（ISK和KLE），并根据不同药物治疗将其分为四组。采用甲基噻唑基二苯基四氮唑溴盐（MTT）法分析ECa细胞系的活力。使用流式细胞仪检测ECa细胞的凋亡情况。为了研究重要蛋白的表达，我们应用了定量实时RT-PCR（qRT-PCR）方法和蛋白质印迹分析。
结果
用THIO加MPA处理后，ECa细胞的活力下调，细胞凋亡上调。THIO+MPA组中孕激素受体B（PRB）和多巴胺受体D2（DRD2）的表达增加，表皮生长因子受体（EGFR）和p-AKT的表达降低。所有这些结果表明，THIO可以促进MPA抑制ECa细胞的生长，尤其是对孕激素抵抗的ECa。
结论
综上所述，本研究的所有数据表明，THIO加MPA可能通过抑制由PRB、DRD2和EGFR介导的PI3K/AKT信号转导途径，作为ECa肿瘤生长的抑制剂。
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