Enchancement of Toremifene Anti-Tumor Action by Metformin and Unusual Side Effect of Toremifene in Male Transgenic Mice with HER2-Positive Breast Tumor.

Autor:	Stukov AN; Department of Innovative Methods of Therapeutic Oncology and Rehabilitation, N. N. Petrov National Medical Research Center of Oncology, St. Petersburg, Russia., Osipov MA; Department of Innovative Methods of Therapeutic Oncology and Rehabilitation, N. N. Petrov National Medical Research Center of Oncology, St. Petersburg, Russia., Semiglazova TY; Department of Innovative Methods of Therapeutic Oncology and Rehabilitation, N. N. Petrov National Medical Research Center of Oncology, St. Petersburg, Russia., Filatova LV; Department of Innovative Methods of Therapeutic Oncology and Rehabilitation, N. N. Petrov National Medical Research Center of Oncology, St. Petersburg, Russia., Alexandrov VA; Laboratory of Cancer Chemoprevention and Oncopharmacology, N. N. Petrov National Medical Research Center of Oncology, St. Petersburg, Russia.; International Research Centre 'Biotechnologies of the Third Millennium', ITMO University, St. Petersburg, Russia., Bespalov VG; Laboratory of Cancer Chemoprevention and Oncopharmacology, N. N. Petrov National Medical Research Center of Oncology, St. Petersburg, Russia.; International Research Centre 'Biotechnologies of the Third Millennium', ITMO University, St. Petersburg, Russia., Semenov AL; Laboratory of Cancer Chemoprevention and Oncopharmacology, N. N. Petrov National Medical Research Center of Oncology, St. Petersburg, Russia.; International Research Centre 'Biotechnologies of the Third Millennium', ITMO University, St. Petersburg, Russia., Tyndyk ML; Laboratory of Carcinogenesis and Aging, N. N. Petrov National Medical Research Center of Oncology, St. Petersburg, Russia., Yurova MN; Laboratory of Carcinogenesis and Aging, N. N. Petrov National Medical Research Center of Oncology, St. Petersburg, Russia., Panchenko AV; Laboratory of Carcinogenesis and Aging, N. N. Petrov National Medical Research Center of Oncology, St. Petersburg, Russia., Baranenko DA; International Research Centre 'Biotechnologies of the Third Millennium', ITMO University, St. Petersburg, Russia.
Jazyk:	angličtina
Zdroj:	Drug research [Drug Res (Stuttg)] 2019 Dec; Vol. 69 (12), pp. 683-687. Date of Electronic Publication: 2019 Sep 24.
DOI:	10.1055/a-0892-4118
Abstrakt:	HER2-positive breast tumors are found in 25-30% of patients with breast cancer and are characterized by aggressive course and reduced sensitivity to both chemotherapy and hormone therapy. The aim of the work was to study the possibilities of enhancing the therapeutic effect of anti-estrogen drug toremifene by combining it with biguanide, metformin, on the HER2-positive breast cancer model in FVB/N HER-2/neu transgenic mouse. Male FBV/N mice with intramuscularly transplanted HER2-positive mammary gland tumor from a female mouse of the same strain have been given toremifene (30 mg/kg, orally daily) or metformin (100 mg/kg, orally daily) that had a moderate antitumor effect (decrease the area under the kinetic curve of tumor growth by 1.6 and 1.5 times, respectively, when compared with intact control). Co-administration of these drugs in the same doses had a more pronounced effect (the area under the kinetic curve of tumor growth decreased by 3.1 times compared to intact control; p<0.05). After 10 days, in group receiving toremifene all 10 mice developed inguinal-scrotal hernias, and in group that received toremifene plus metformin - only 5 of 10 (p=0.0325). By the 15 th day after the start of treatment, the hernias was also determined in all mice treated with the combination of toremifene and metformin, but the size of the hernial sac was significantly smaller than in those receiving only toremifene - 537 ± 96 mm 3 and 1309 ± 120 mm 3 , respectively (p=0.0001). A possible explanation is the manifestation of collagen-degrading effect of toremifene. Competing Interests: The authors declare that there is no conflict of interest. (© Georg Thieme Verlag KG Stuttgart · New York.)
Databáze:	MEDLINE
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