Characterization of somatostatin receptors and growth inhibition by the somatostatin analogue BIM23014 in small cell lung carcinoma xenograft: SCLC-6

Abstract

Human small cell lung cancer (SCLC) is a neuroendocrine tumour with a very poor prognostic. Receptors for somatostatin-14 and its synthetic analogue BIM23014 (Lanreotide) were characterized in 3 human SCLC xenografts (SCLC-6, SCLC-10 and SCLC-75) transplanted in nude mice. The binding activity of both iodinated ligands was tested by cross-linking assay. One major complex of 57kDa was identified by both ligands in all 3 tumours. Two other minor complexes were only detected by the natural ligand: 90kDa in all 3 tumours and 70kDa in 2 out of the 3 tumours (SCLC-6 and SCLC-75). Analysed by Northern hydrization, the expression of the gene encoding for the receptor subtype I was detected in all 3 tumours whereas the expression of the receptor subtype II was only detected in 2 out of the 3 tumours (SCLC-6 and SCLC-75). No receptor subtype III transcript was observed. The relative quantification of the detected messengers and of the cross-linked complexes determined by densitometry suggested that SCLC-6 contained a large amount of somatostatin receptors. SCLC-6 growing in nude mice was used to evaluate the antiproliferative effect of BIM23014. BIM23014 (250μg, b. i. d. for 5 days) significantly inhibited tumor growth and had an additive effect with cis-platinum (1.5mg/ kg/day for 2 days) when given concomitantly. Values of the relative tumour volume as compared to control were: BIM23014 alone 57%, cis-platinum alone 57% and BIM23014 + cis-platinum: 78%. These experimental data suggest that BIM23014 given alone or in combination with cis-platinum could have a therapeutic potential in the treatment of somatostatin receptor positive SCLCs.