Growth-inhibitory effect of adiponectin via adiponectin receptor 1 on human breast cancer cells through inhibition of S-phase entry without inducing apoptosis
Growth-inhibitory effect of adiponectin via adiponectin receptor 1 on human breast cancer cells through inhibition of S-phase entry without inducing apoptosis
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DOI：
10.1007/s10549-007-9874-3
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发表时间：
2008-12-01
影响因子：
3.8
通讯作者：
Noguchi, Shinzaburo
中科院分区：
文献类型：
--
作者：
Nakayama, Satoshi;Miyoshi, Yasuo;Noguchi, Shinzaburo
脂联素是脂肪组织分泌的最重要的脂肪细胞因子之一。据报道，脂联素除了对葡萄糖和脂肪酸代谢有影响外，还对乳腺癌细胞有直接的生长抑制作用。然而，脂联素如何影响细胞周期和细胞凋亡，以及其抑制作用是否通过脂联素受体介导，仍有待进一步研究。在这里，我们证明了脂联素处理导致了显著的剂量依赖的抑制生长的MDA-MB-231和T47D细胞。脂联素处理后，两株细胞的G0/G1期细胞数均显著增加，但未诱导细胞凋亡。脂联素受体1的mRNA和蛋白在两种细胞中均有高表达，而脂联素受体2的表达很低。用针对脂联素受体1的小干扰RNA显著减轻脂联素对两种细胞的生长抑制作用。综上所述，脂联素通过抑制乳腺癌细胞进入S期而不诱导细胞凋亡，从而抑制乳腺癌细胞的增殖，这种抑制作用是通过脂联素受体1介导的。
Adiponectin is one of the most important adipocytokines secreted from adipose tissue. In addition to its effects on glucose and fatty acid metabolism, it has been reported that adiponectin has a direct growth-inhibitory effect on breast cancer cells. However, it still remains to be established how adiponectin affects cell cycle and apoptosis and whether or not its inhibitory effect is mediated through adiponectin receptors. Here, we demonstrated that adiponectin treatment resulted in a significant dose-dependent growth inhibition of both MDA-MB-231 and T47D cells. In both cell lines, the G0/G1 population significantly increased after adiponectin treatment, but apoptosis was not induced. High expression of mRNA and protein of adiponectin receptor 1 was observed, but expression of adiponectin receptor 2 was very low in both cell lines. Treatment with small interference RNA against adiponectin receptor 1 significantly reduced the growth inhibition induced by adiponectin in both cell lines. Taken together, adiponectin decreases breast cancer cell proliferation by inhibiting the entry into S-phase without inducing apoptosis, and this inhibitory effect is mediated through adiponectin receptor 1.