Peripheral Opioid Antagonist Enhances the Effect of Anti-Tumor Drug by Blocking a Cell Growth-Suppressive Pathway In Vivo
Fig 2
Blockade of OGF signaling by methylnaltrexone (MNTX) increased the growth of a diffuse-type GC cell line, but not an intestinal-type GC cell line, under low nutrient conditions.
A, RT-PCR analyses of PENK and OGFR in diffuse-type GC cell lines, HSC-60 cells and highly metastatic 60As6 cells, 60As6 xenograft (60As6 xeno) and the intestinal-type GC cell line HSC-42. B, growth of 60As6 cells treated with OGF (10-4 M), methylnaltrexone (MNTX, 10-6 M), or a combination of these compounds for 72 h (mean ± SD, n = 3–6 per group, *p<0.05, control vs. OGF, #p <0.05, OGF vs. OGF/MNTX). C, western blot analysis of OGFR protein in 60As6 cells with a stable transfectant of OGFR shRNA or control shRNA. D, growth of the stable transfectant of OGFR shRNA of 60As6 cells in the presence or absence of OGF (10-4 M) for 72 h. Non-targeting control shRNA was used as a control (mean ± SD, n = 3 each). Growth of 60As6 cells (E) and HSC-42 cells (F) treated with MNTX (10-6 and 10-5 M) or a vehicle for 72 h under normal nutrient (10% FBS) and low nutrient (2% FBS) conditions. (mean ± SD, n = 4 each, *p<0.05, vs. control).