Adiponectin inhibits the growth and peritoneal metastasis of gastric cancer through its specific membrane receptors AdipoR1 and AdipoR2
Adiponectin inhibits the growth and peritoneal metastasis of gastric cancer through its specific membrane receptors AdipoR1 and AdipoR2
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DOI：
10.1111/j.1349-7006.2007.00486.x
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发表时间：
2007-07-01
期刊：
影响因子：
5.7
通讯作者：
Nagawa, Hirokazu
中科院分区：
文献类型：
--
作者：
Ishikawa, Makoto;Kitayama, Joji;Nagawa, Hirokazu
脂联素是一种在脂肪组织中产生的循环肽类激素，在癌症患者的血浆中已被证明是减少的，这表明这种脂肪因子可能机械地参与了与肥胖相关的癌症发生的发病机制。在这项研究中，我们检测脂联素受体（AdipoR 1和AdipoR 2）的表达，并评估脂联素在胃癌中的作用。6种胃癌细胞株均表达两种受体的mRNA和蛋白，但表达水平不同。添加30 μ g/mL脂联素可有效诱导AZ 521和HCG 27细胞凋亡并抑制其增殖。通过特异性siRNA下调AdipoR 1或AdipoR 2显著抑制了脂联素在两种细胞系中的生长抑制作用。局部注射脂联素可明显抑制裸鼠皮下接种的AZ 521细胞的生长。同样，持续腹腔内输注脂联素有效地抑制了AZ 521腹膜转移的发展。脂联素可能通过AdipoR 1和AdipoR 2负调控胃癌细胞的生长。虽然脂联素已被报道具有抗血管生成作用，我们的研究结果表明，脂联素的抗肿瘤作用，至少部分依赖于对肿瘤细胞的直接影响。
Adiponectin, a circulating peptide hormone produced in adipose tissue, has been shown to be reduced in the plasma of patients with cancer, suggesting that this adipokine may be mechanically involved in the pathogenesis of adiposity-related carcinogenesis. In this study, we examined the expression of adiponectin receptors (AdipoR1 and AdipoR2) and assessed the function of adiponectin in gastric cancer. All of the six gastric cancer cell lines significantly expressed mRNA and protein of both receptors with variable levels. Addition of 30 mu g/mL adiponectin potently induced apoptosis and inhibited the proliferation of AZ521 and HCG27. Down-regulation of either AdipoR1 or AdipoR2 by specific siRNA significantly suppressed the growth inhibitory effects of adiponectin in both cell lines. Moreover, a local injection of adiponectin markedly inhibited the growth of AZ521 inoculated subcutaneously in nude mice. Similarly, the continuous intraperitoneal infusion of adiponectin effectively suppressed the development of peritoneal metastasis of AZ521. Adiponectin negatively regulates the progression of gastric cancer cells possibly through both AdipoR1 and AdipoR2. Although adiponectin was already reported to have antiangiogenic effects, our results suggest that the antitumor effect of adiponectin was, at least partially, dependent on the direct effects on tumor cells.