The role of hormones and aromatase inhibitors on breast tumor growth and general health in a postmenopausal mouse model

Reproductive Biology and Endocrinology

Rajkumar Lakshmanaswamy¹  Elaine A Lissner²  Arunkumar Arumugam¹ 

[1] Center of Excellence in Cancer Research, Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, Texas 79905, USA;Parsemus Foundation, Berkeley, California 94702, USA

关键词: Cardiac markers;    Bone markers;    Hormones;    Aromatase inhibitors;    Postmenopausal breast cancer;   

Others  :  1139789
DOI  :  10.1186/1477-7827-12-66

 received in 2014-04-04, accepted in 2014-06-17,  发布年份 2014

【 摘 要 】

Background

Breast cancer is the most frequently diagnosed cancer in women in the United States. Approximately 70% of breast cancers are diagnosed in postmenopausal women. Major clinical trials and experimental studies showed that aromatase inhibitors are effective against postmenopausal breast cancer. Despite their effectiveness in reducing tumor recurrence, aromatase inhibitors have adverse effects on the cardiovascular system and increase osteoporosis and bone fractures. Our study is aimed at investigating the role of natural steroid hormones on serum cardiovascular and bone resorption markers in an established mouse model mimicking postmenopausal breast cancer.

Methods

Ovariectomized nude mice were transplanted with MCF-7 breast cancer cells constitutively expressing aromatase. The mice were treated with different combinations and doses of steroids, [estrogen (25 pg, 40 pg, 100 pg), progesterone (6 ng) and testosterone (50 ng)] along with dehydroepiandrostenedione (100 ug). Serum levels of HDL, LDL/VLDL, free and total cholesterol, total and bone specific alkaline phosphatase and triglycerides were analyzed after 5, 10 and 15 months.

Results

Free cholesterol and LDL/VLDL levels in serum were reduced in groups mimicking estrous cycle and menstrual cycle hormones treatment. HDL cholesterol was increased in all the hormone treated groups except the estrous cycle-mimicking group. Bone specific alkaline phosphatase was decreased in menstrual cycle levels of estrogen and progesterone treatment.

Conclusions

All together our results show that use of natural hormones in appropriate combinations have beneficial effects on cardiac and bone toxicity, along with better tumor reduction than current treatments.

【 授权许可】

   
2014 Arumugam et al.; licensee BioMed Central Ltd.

【 图 表 】

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