RETINOID-INDUCED DIFFERENTIATION OF NEUROBLASTOMA - COMPARISON BETWEEN LG69, AN RXR-SELECTIVE ANALOG AND 9-CIS RETINOIC ACID

The aim of this study was to investigate in vitro the effects of all-t rans retinoic acid (RA), 9-cis RA and the RXR-selective analogue, LG69 , on the morphological differentiation, proliferation and gene express ion of neuroblastoma cells. Three different cell lines were cultured w ith the retinoid for either 9 continuous days or for 5 days followed b y 4 days without the retinoid and morphological differentiation was as sessed both qualitatively and quantitatively. SR SY 5Y cell proliferat ion was examined by measuring cell numbers after exposure to the retin oids and RAR-beta gene expression was examined by Northern blot analys is. Morphological differentiation was more effectively induced by all- trans and 9-cis PA than by LG69. SH SY 5Y cells, when treated with 9-c is RA for only 5 of the 9 days of culture, underwent apoptosis, but th is was not seen with 9 days continuous exposure nor with LG69. Inhibit ion of SR SY 5Y cell proliferation by all-trans or 9-cis RA was dose-d ependent, but LG69 had little effect. Conversely, LG69 induced higher expression of RAR-beta than all-trans RA, but less than that produced by 9-cis RA. These data suggest that 9-cis RA as a single agent is the most effective modulator of neuroblastoma behaviour and may be the mo st appropriate therapeutic agent. (C) 1998 Elsevier Science Ltd.