Enhanced cytotoxicity and apoptosis by raloxifene in combination with estrogen and methotrexate in human endometrial stromal cells

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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.

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