Effects of adiponectin and leptin co-treatment on human breast cancer cell growth
Effects of adiponectin and leptin co-treatment on human breast cancer cell growth
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DOI：
10.3892/or_00000395
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发表时间：
2009-06-01
期刊：
影响因子：
4.2
通讯作者：
Cleary, Margot P.
中科院分区：
文献类型：
--
作者：
Nkhata, Katai J.;Ray, Amitabha;Cleary, Margot P.
肥胖是绝经后乳腺癌（BC）的一个危险因素，但这种关系的具体机制尚不清楚。对脂肪细胞源性脂联素和瘦素的研究揭示了它们在体外对BC细胞增殖的相反作用，表明它们可能在BC发病机制中起作用。在当前的研究中，我们检查了用不同脂联素：瘦素（A/L）比例处理的五种BC细胞系的增殖影响。MCF-7和T47-D细胞的增殖随着比率增加（2-500）而降低，而在类似处理的MDA-MB-231和MDA-MB-361细胞中观察到增殖增加。对于SK-BR-3细胞。上升的比率为8。我们确定了在所有A/L比为100的情况下处理的MCF-7和T47-D细胞中对一些促有丝分裂、存活和凋亡相关蛋白的差异效应。MCF-7细胞中AKT和MAPK通路未被激活，而T47-D细胞中AKT激活在30 min内发生，MAPK激活持续到48 h。p53和Bax在MCF-7中升高，但在30分钟时在T47-D细胞中低于基础值。虽然共处理增强MCF-7中的凋亡，但类似的处理在T47-D细胞中具有相反的效果。MCF-7和T47-D处理前后细胞周期分布无明显差异。联合处理后T47-D细胞G1/G 0期比例略高。由于不同细胞系对A/L比值的反应不同，A/L比值对细胞增殖的影响可能具有一定的特异性。这可能解释了以前血清瘦素与BC关系的不一致性。需要更多的研究来更好地了解这两种脂肪因子之间存在的复杂相互作用。
Obesity is a risk factor for postmenopausal breast cancer (BC), but the specific mechanisms for this relationship are not well understood. Studies on adipocyte-derived adiponectin and leptin reveal opposing effects oil BC cell proliferation in vitro, suggesting they may play a role in BC pathogenesis. In the Current Study we examined effects oil proliferation of five BC cell lines treated with varying adiponectin:leptin (A/L) ratios. A decrease in proliferation was noted for MCF-7 and T47-D cells with increasing ratios (2-500), while an increase was seen in similarly treated MDA-MB-231 and MDA-MB-361 cells. For SK-BR-3 cells. an increase was seen at a ratio of 8. We identified differential effects on some pro-mitogenic, survival and apoptosis-related proteins in MCF-7 and T47-D cells treated at all A/L ratio of 100. Specifically, the AKT and MAPK pathways were not activated ill MCF-7 cells, but AKT activation occured within 30 min and MAPK activation was sustained at 48 h in T47-D cells. p53 and Bax were elevated in MCF-7, but were below basal in T47-D cells at 30 min. While co-treatment enhanced apoptosis in MCF-7, similar treatment had the opposite effect in T47-D cells. There were no differences in cell cycle distribution between treated Or untreated MCF-7 or T47-D. although T47-D cells had it slightly higher proportion in the G1/G0 phase after co-treatment. The effects of A/L ratio on mediating proliferation may have some specificity since the cell lines exhibited different responses. This may explain previous inconsistencies for the relationship of serum leptin with BC. More Studies are needed to better understand the complex interactions that exist between these two adipokines.