Fukumoto Keiko, Yano Yoshihisa, Virgona Nantiga, Hagiwara Hiromi, Sato Hiromi, Senba Hironobu, Suzuki Kazuyuki, Asano Ryuji, Yamada Kazuhiko, Yano Tomohiro
Department of Food Science Research for Health, National Institute of Health and Nutrition, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8636, Japan.
FEBS Lett. 2005 Jul 4;579(17):3829-36. doi: 10.1016/j.febslet.2005.06.004.
It has been assumed that prostaglandin (PG)I2 signaling contributes to the negative growth control of lung cancer cells; however, the mechanism remains unresolved. PGI2 functions through a cell surface G protein-coupled receptor (prostaglandin I2-binding receptor, IP) and also exerts an effect by interacting with a nuclear hormone receptor, peroxisome proliferator-activated receptor delta (PPARdelta). We found that PPARdelta was a key molecule of PGI2 signaling to give negative growth control of lung cancer cells (A549), using carbarprostacyclin, a PGI2 agonist for IP and PPARdelta, and L-165041, a PPARdelta agonist. Furthermore, PPARdelta-induced cell growth control was reinforced by the inhibition of cyclooxygenase. These results suggest that PPARdelta activation under the suppression of PG synthesis is important to regulate lung cancer cell growth.
人们一直认为前列腺素（PG）I2信号传导有助于肺癌细胞的负生长控制；然而，其机制仍未得到解决。PGI2通过细胞表面G蛋白偶联受体（前列腺素I2结合受体，IP）发挥作用，也通过与核激素受体过氧化物酶体增殖物激活受体δ（PPARδ）相互作用发挥作用。我们发现，使用IP和PPARδ的PGI2激动剂卡前列环素以及PPARδ激动剂L-165041，PPARδ是PGI2信号传导中对肺癌细胞（A549）进行负生长控制的关键分子。此外，环氧化酶的抑制增强了PPARδ诱导的细胞生长控制。这些结果表明，在PG合成受抑制的情况下激活PPARδ对于调节肺癌细胞生长很重要。
