{"title":"在激素依赖性乳腺癌细胞模型中,高葡萄糖降低芳香化酶抑制剂的抗肿瘤活性","authors":"Kamila Boszkiewicz, Agnieszka Piwowar","doi":"10.32383/appdr/168363","DOIUrl":null,"url":null,"abstract":"One third of breast cancer patients also suffer from diabetes, which is associated with a 40% higher risk of mortality. Patients undergoing anti-cancer treatment are also exposed to xenoestrogens present in everyday life, which may affect the effectiveness of the therapies used. The purpose of our study was to analyzed the effect of metalloestrogens (Al, Cr[III]) on the effectiveness of aromatase inhibitors (AIs) under high glucose conditions prevailing in the cellular model. On two human breast cancer cell lines—MCF-7 and MCF-7/DOX—a cell viability assay, a flow cytometer analysis of apoptosis, and protein activity of BAX, Bcl-2, and VEGF-A by ELISA were carried out. Results were analyzed using one-way ANOVA, followed post hoc by Tukey’s multiple comparisons tests. High glucose conditions reduced the effectiveness of AIs in both cell lines (decreased cytotoxicity, inhibition of apoptosis, increase in Bcl-2/BAX ratio and angiogenesis), regardless of the combination with metalloestrogens. Hyperglycemia may affect the effectiveness of AIs to a greater extent than metalloestrogens alone - the activity of drugs in the presence of high glucose concentrations was significantly lower, regardless of the combination with metalloestrogens, which indicates the key role of hyperglycemia in attenuating their activity. Therefore controlling hyperglycemia and individualized treatment regimens in cancer patients with diabetes may have important therapeutic implications.","PeriodicalId":7147,"journal":{"name":"Acta poloniae pharmaceutica","volume":null,"pages":null},"PeriodicalIF":0.4000,"publicationDate":"2023-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"High glucose reduces anti-tumor activity of aromatase inhibitors in a hormone-dependent breast cancer cell model\",\"authors\":\"Kamila Boszkiewicz, Agnieszka Piwowar\",\"doi\":\"10.32383/appdr/168363\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"One third of breast cancer patients also suffer from diabetes, which is associated with a 40% higher risk of mortality. Patients undergoing anti-cancer treatment are also exposed to xenoestrogens present in everyday life, which may affect the effectiveness of the therapies used. The purpose of our study was to analyzed the effect of metalloestrogens (Al, Cr[III]) on the effectiveness of aromatase inhibitors (AIs) under high glucose conditions prevailing in the cellular model. On two human breast cancer cell lines—MCF-7 and MCF-7/DOX—a cell viability assay, a flow cytometer analysis of apoptosis, and protein activity of BAX, Bcl-2, and VEGF-A by ELISA were carried out. Results were analyzed using one-way ANOVA, followed post hoc by Tukey’s multiple comparisons tests. High glucose conditions reduced the effectiveness of AIs in both cell lines (decreased cytotoxicity, inhibition of apoptosis, increase in Bcl-2/BAX ratio and angiogenesis), regardless of the combination with metalloestrogens. Hyperglycemia may affect the effectiveness of AIs to a greater extent than metalloestrogens alone - the activity of drugs in the presence of high glucose concentrations was significantly lower, regardless of the combination with metalloestrogens, which indicates the key role of hyperglycemia in attenuating their activity. Therefore controlling hyperglycemia and individualized treatment regimens in cancer patients with diabetes may have important therapeutic implications.\",\"PeriodicalId\":7147,\"journal\":{\"name\":\"Acta poloniae pharmaceutica\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.4000,\"publicationDate\":\"2023-07-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Acta poloniae pharmaceutica\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.32383/appdr/168363\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta poloniae pharmaceutica","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.32383/appdr/168363","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
High glucose reduces anti-tumor activity of aromatase inhibitors in a hormone-dependent breast cancer cell model
One third of breast cancer patients also suffer from diabetes, which is associated with a 40% higher risk of mortality. Patients undergoing anti-cancer treatment are also exposed to xenoestrogens present in everyday life, which may affect the effectiveness of the therapies used. The purpose of our study was to analyzed the effect of metalloestrogens (Al, Cr[III]) on the effectiveness of aromatase inhibitors (AIs) under high glucose conditions prevailing in the cellular model. On two human breast cancer cell lines—MCF-7 and MCF-7/DOX—a cell viability assay, a flow cytometer analysis of apoptosis, and protein activity of BAX, Bcl-2, and VEGF-A by ELISA were carried out. Results were analyzed using one-way ANOVA, followed post hoc by Tukey’s multiple comparisons tests. High glucose conditions reduced the effectiveness of AIs in both cell lines (decreased cytotoxicity, inhibition of apoptosis, increase in Bcl-2/BAX ratio and angiogenesis), regardless of the combination with metalloestrogens. Hyperglycemia may affect the effectiveness of AIs to a greater extent than metalloestrogens alone - the activity of drugs in the presence of high glucose concentrations was significantly lower, regardless of the combination with metalloestrogens, which indicates the key role of hyperglycemia in attenuating their activity. Therefore controlling hyperglycemia and individualized treatment regimens in cancer patients with diabetes may have important therapeutic implications.
期刊介绍:
The international journal of the Polish Pharmaceutical Society is published in 6 issues a year. The journal offers Open Access publication of original research papers, short communications and reviews written in English, in all areas of pharmaceutical sciences. The following areas of pharmaceutical sciences are covered: Analysis, Biopharmacy, Drug Biochemistry, Drug Synthesis, Natural Drugs, Pharmaceutical Technology, Pharmacology and General.
A bimonthly appearing in English since 1994, which continues “Acta Poloniae Pharmaceutica”, whose first issue appeared in December 1937. The war halted the activity of the journal’s creators. Issuance of “Acta Poloniae Pharmaceutica” was resumed in 1947. From 1947 the journal appeared irregularly, initially as a quarterly, then a bimonthly. In the years 1963 – 1973 alongside the Polish version appeared the English edition of the journal. Starting from 1974 only works in English are published in the journal. Since 1995 the journal has been appearing very regularly in two-month intervals (six books a year). The journal publishes original works from all fields of pharmacy, summaries of postdoctoral dissertations and laboratory notes.