CAI inhibits the growth of small cell lung cancer cells.

The effects of carboxyamido-triazole (CAI) on small cell lung cancer (SCLC) cells were investigated. Using SCLC cell lines NCI-H209 or H345, 20 micro M CAI had little effect on basal cytosolic Ca(2+) but inhibited the ability of 10 nM bombesin (BB) or 1 nM neurotensin (NT) to elevate cytosolic Ca(2+). Also, CAI, impaired the ability of BB or NT to cause tyrosine phosphorylation of focal adhesion kinase. In contrast, CAI did not affect the ability of (125I-Tyr(4))BB or 125I-NT to bind with high affinity to NCI-H345 cells. These results indicate that CAI impairs SCLC second messenger activation, but not neuropeptide receptor binding. Using a MTT growth assay, CAI inhibited the proliferation of NCI-H209 or H345 cells in a concentration-dependent manner with little proliferation occurring using 100 micro M CAI. Also, CAI inhibited colony formation of NCI-H209 or H345 cells in a dose-dependent manner in vitro. In vivo, CAI (2 mg/day by gavage) inhibited significantly NCI-H209 xenograft proliferation in nude mice. Animals treated daily with CAI had significantly reduced CD31 immunostaining of microvessels in the tumor. Also, CAI inhibited the increase in vascular endothelial cell growth factor (VEGF) mRNA after addition of BB to SCLC cells. These results suggest that CAI inhibits the growth of SCLC cells as well as the angiogenesis of SCLC tumors in a VEGF-dependent manner.