Ishikawa Makoto, Kitayama Joji, Yamauchi Toshimasa, Kadowaki Takashi, Maki Toshiyuki, Miyato Hideyo, Yamashita Hiroharu, Nagawa Hirokazu
Department of Surgical Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Cancer Sci. 2007 Jul;98(7):1120-7. doi: 10.1111/j.1349-7006.2007.00486.x. Epub 2007 Apr 23.
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 microg/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.
脂联素是一种在脂肪组织中产生的循环肽激素,研究表明癌症患者血浆中的脂联素水平降低,提示这种脂肪因子可能在肥胖相关致癌作用的发病机制中发挥作用。在本研究中,我们检测了脂联素受体(AdipoR1和AdipoR2)的表达,并评估了脂联素在胃癌中的功能。六种胃癌细胞系均显著表达两种受体的mRNA和蛋白,但表达水平各不相同。添加30μg/mL脂联素可有效诱导AZ521和HCG27细胞凋亡并抑制其增殖。用特异性siRNA下调AdipoR1或AdipoR2可显著抑制脂联素对这两种细胞系的生长抑制作用。此外,局部注射脂联素可显著抑制皮下接种于裸鼠的AZ521细胞生长。同样,持续腹腔内输注脂联素可有效抑制AZ521细胞腹膜转移的发生。脂联素可能通过AdipoR1和AdipoR2负向调节胃癌细胞的进展。尽管此前已有报道脂联素具有抗血管生成作用,但我们的结果表明,脂联素的抗肿瘤作用至少部分依赖于对肿瘤细胞的直接作用。