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胰高血糖素样肽-1受体激动剂对肥胖相关乳腺癌的抗增殖活性：对调节脂肪细胞和癌细胞中脂肪因子表达的影响。

Anti-Proliferative Activity of Glucagon-Like Peptide-1 Receptor Agonist on Obesity-Associated Breast Cancer: The Impact on Modulating Adipokines' Expression in Adipocytes and Cancer Cells.

作者信息

Alanteet Alaa A, Attia Hala A, Shaheen Sameerah, Alfayez Musaed, Alshanawani Bisher

机构信息

Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.

Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.

出版信息

Dose Response. 2021 Feb 22;19(1):1559325821995651. doi: 10.1177/1559325821995651. eCollection 2021 Jan-Mar.

DOI:10.1177/1559325821995651
PMID:33746653
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7903831/
Abstract

Obesity is associated with high risk and poor prognosis of breast cancer (BC). Obesity promotes BC cells proliferation via modulating the production of adipokines, including adiponectin (anti-neoplastic adipokine), leptin (carcinogenic adipokine) and inflammatory mediators. In the present study we investigated the anti-proliferative effects of liraglutide (LG; anti-diabetic and weight reducing drug) on MCF-7 human BC cells cultured in obese adipose tissue-derived stem cells-conditioned medium (ADSCs-CM) and whether this effect is mediated via modulating the adipokines in ADSCs and cancer cells. Proliferation was investigated using AlamarBlue viability test, colony forming assay and cell cycle analysis. Levels and expression of adipokines and their receptors were assayed using ELISA and RT-PCR. LG caused 48% inhibition of MCF-7 proliferation in obese ADSCs-CM, reduced the colony formation and induced G0/G1 phase arrest. LG also decreased the levels of inflammatory mediators, suppressed the expression of leptin, while increased mRNA levels of adiponectin and their receptors in obese ADSCs and cancer cells cultured in obese ADCSs-CM. In conclusion, LG could mitigate BC cell growth in obese subjects; therefore it could be used for clinical prevention and/or treatment of BC in obese subjects. It may assist to improve treatment outcomes and, reduce the mortality rate in obese patients with BC.

摘要

肥胖与乳腺癌（BC）的高风险和不良预后相关。肥胖通过调节脂肪因子的产生促进BC细胞增殖，这些脂肪因子包括脂联素（抗肿瘤脂肪因子）、瘦素（致癌脂肪因子）和炎症介质。在本研究中，我们研究了利拉鲁肽（LG；抗糖尿病和减肥药物）对在肥胖脂肪组织来源的干细胞条件培养基（ADSCs-CM）中培养的MCF-7人BC细胞的抗增殖作用，以及这种作用是否通过调节ADSCs和癌细胞中的脂肪因子来介导。使用AlamarBlue活力测试、集落形成试验和细胞周期分析来研究增殖情况。使用ELISA和RT-PCR测定脂肪因子及其受体的水平和表达。LG在肥胖ADSCs-CM中对MCF-7增殖产生48%的抑制作用，减少集落形成并诱导G0/G1期阻滞。LG还降低了炎症介质的水平，抑制了瘦素的表达，同时增加了肥胖ADSCs和在肥胖ADCSs-CM中培养的癌细胞中脂联素及其受体的mRNA水平。总之，LG可以减轻肥胖受试者的BC细胞生长；因此它可用于肥胖受试者BC的临床预防和/或治疗。它可能有助于改善治疗效果，并降低肥胖BC患者的死亡率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d4a/7903831/968392ed3b62/10.1177_1559325821995651-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d4a/7903831/ec75383dd014/10.1177_1559325821995651-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d4a/7903831/4d8e05e4c1d2/10.1177_1559325821995651-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d4a/7903831/8e7131bcd7b7/10.1177_1559325821995651-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d4a/7903831/05d6d3ee519b/10.1177_1559325821995651-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d4a/7903831/fdf12a946479/10.1177_1559325821995651-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d4a/7903831/45250de908aa/10.1177_1559325821995651-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d4a/7903831/968392ed3b62/10.1177_1559325821995651-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d4a/7903831/ec75383dd014/10.1177_1559325821995651-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d4a/7903831/4d8e05e4c1d2/10.1177_1559325821995651-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d4a/7903831/8e7131bcd7b7/10.1177_1559325821995651-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d4a/7903831/05d6d3ee519b/10.1177_1559325821995651-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d4a/7903831/fdf12a946479/10.1177_1559325821995651-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d4a/7903831/45250de908aa/10.1177_1559325821995651-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d4a/7903831/968392ed3b62/10.1177_1559325821995651-fig7.jpg

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