Enhanced cytotoxicity and apoptosis by raloxifene in combination with estrogen and methotrexate in human endometrial stromal cells,Chemical Biology & Drug Design

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Enhanced cytotoxicity and apoptosis by raloxifene in combination with estrogen and methotrexate in human endometrial stromal cells
Chemical Biology & Drug Design ( IF 3.2 ) Pub Date : 2017-12-15 , DOI: 10.1111/cbdd.13152
Ivana Nikolic ₁ , Marija Andjelkovic ₁ , Milan Zaric ₁ , Ivanka Zelen ₁ , Zoran Milosavljevic ₂ , Petar Canovic ₁ , Marina Mitrovic ₁

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Endometrial hyperplasia is a condition that may lead to the development of endometrial carcinoma. Initially, changes of the endometrium are caused by the estrogen's hyperstimulation that may lead to the development of an irregular bleeding and the infertility problems. Therapy of endometrial hyperplasia is limited to medical and surgical approaches. During the past decade, the new types of drugs were developed for the treatment of the endometrial hyperplasia. Here, for the first time, we investigated the cytotoxic effects of the various combinations of estrogen, raloxifene, and methotrexate in human ThESC cell line as a possible potential treatment of the endometrial hyperplasia. Our aim was to investigate and to determine the most efficient combination of investigated drugs in ThESC cells during 24‐hr period using MTT assay, FACS analysis, and immunofluorescence staining. Our results demonstrated that the combination of raloxifene with methotrexate efficiently induced both the cytotoxicity and apoptosis in ThESC cells when compared to their single effect, as well as to the effect of combined treatment of raloxifene with estrogen. The application of the low doses of methotrexate combined with raloxifene offers all advantages of a potential beneficial antitumor match in cancer chemoprevention and therapy.

中文翻译：

雷洛昔芬联合雌激素和甲氨蝶呤在人子宫内膜间质细胞中增强的细胞毒性和凋亡

子宫内膜增生是可能导致子宫内膜癌发展的疾病。最初，子宫内膜的变化是由雌激素的过度刺激引起的，可能导致不规则出血和不孕症的发展。子宫内膜增生的治疗仅限于医学和外科手术方法。在过去的十年中，开发了用于治疗子宫内膜增生的新型药物。在这里，我们首次研究了雌激素，雷洛昔芬和甲氨蝶呤的各种组合在人ThESC细胞系中的细胞毒性作用，以作为可能治疗子宫内膜增生的方法。我们的目的是使用MTT分析，FACS分析，和免疫荧光染色。我们的结果表明，雷洛昔芬与甲氨蝶呤的组合与单作用以及与雌激素联合治疗雷洛昔芬的作用相比，能有效地诱导ThESC细胞的细胞毒性和凋亡。低剂量甲氨蝶呤联合雷洛昔芬的应用具有在癌症化学预防和治疗中潜在有益的抗肿瘤匹配的所有优点。

更新日期：2017-12-15

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