Auzoux-Bordenave Stéphanie, Solvar Marthe, Queguiner Isabelle, Bozzolan Françoise, Mottier Violaine, Siaussat David, Porcheron Patrick, Debernard Stéphane
UMR 1272 Physiologie de l'insecte: Signalisation et Communication, Université Pierre et Marie Curie, 12 rue Cuvier, 75005 Paris, France.
Insect Biochem Mol Biol. 2005 Sep;35(9):1033-42. doi: 10.1016/j.ibmb.2005.04.004.
The non-steroidal ecdysone agonist, RH-5992, exhibits ecdysteroid activities in vivo as well as in vitro more effectively than 20-hydroxyecdysone (20E). Using the IAL-PID2 cells derived from imaginal wing discs of last larval instar of Plodia interpunctella, we investigated the action of RH-5992 in the control of cell growth. Its effects on the proliferative activity of IAL-PID2 cells, the induction level in G2/M arrest and on the expression rate of Plodia B cyclin (PcycB), ecdysone B1-isoform (PIEcR-B1) and Ultraspiracle-2 isoform (PIUSP-2) were examined. From these cellular and molecular assays, our results brought evidence that RH-5992, like 20E, induced an inhibition on cell proliferation by blocking IAL-PID2 cells in G2/M phase. Moreover, this G2/M arrest was preceded by a decrease in the expression level of PcycB and a high induction of PIEcR-B1, PIUSP-2 mRNAs. Dose-response experiments revealed that RH-5992 was even more potent than 20E. On these parameters, we therefore suggest that the differential observed in the expression level of USP and EcR by RH-5992 and 20E could contribute to the difference observed for the biological potency of these two compounds.
非甾体类蜕皮激素激动剂RH - 5992在体内和体外均表现出比20 - 羟基蜕皮激素（20E）更有效的蜕皮甾体活性。利用来源于印度谷螟末龄幼虫翅芽的IAL - PID2细胞，我们研究了RH - 5992在控制细胞生长中的作用。检测了其对IAL - PID2细胞增殖活性、G2/M期阻滞诱导水平以及印度谷螟B型细胞周期蛋白（PcycB）、蜕皮激素B1亚型（PIEcR - B1）和超气门蛋白-2亚型（PIUSP - 2）表达率的影响。从这些细胞和分子检测结果来看，我们的研究结果表明，与20E一样，RH - 5992通过使IAL - PID2细胞阻滞于G2/M期来抑制细胞增殖。此外，在这种G2/M期阻滞之前，PcycB的表达水平下降，PIEcR - B1、PIUSP - 2 mRNA高度诱导。剂量反应实验表明，RH - 5992比20E更有效。基于这些参数，我们因此认为，RH - 5992和20E在USP和EcR表达水平上观察到的差异可能导致了这两种化合物在生物学活性上观察到的差异。
