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.
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.
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DOI：
10.1177/1559325821995651
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Alshanawani B
中科院分区：
文献类型：
--
作者：
Alanteet AA;Attia HA;Shaheen S;Alfayez M;Alshanawani B
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，所述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ADSC和癌细胞中的脂肪因子介导。采用AlamarBlue活力试验、集落形成试验和细胞周期分析研究增殖。采用ELISA和RT-PCR检测脂肪因子及其受体的水平和表达。LG对肥胖ADSCs-CM中MCF-7的增殖抑制率为48%，并可使殖民地形成减少，使细胞阻滞于G 0/G1期。LG还降低了肥胖ADSCs和肥胖ADCS-CM中培养的癌细胞中炎症介质的水平，抑制了瘦素的表达，同时增加了脂联素及其受体的mRNA水平。总之，LG可以减轻肥胖受试者中的BC细胞生长;因此，它可以用于肥胖受试者中BC的临床预防和/或治疗。它可能有助于改善治疗结果，降低肥胖BC患者的死亡率。
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.
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