SOMATOSTATIN ANALOG OCTREOTIDE INHIBITS THE GROWTH OF DIFFERENTIATED THYROID-CANCER CELLS IN-VITRO, BUT NOT IN-VIVO

Somatostatin and its analogs are antiproliferative in a wide range of normal and neoplastic tissues. In this study we investigated the effec t of octreotide (SMS 201-995) on the invasion and growth of three foll icular thyroid cancer (FTC) cell lines from one patient in vitro and i n vivo. FTC133 was established from the primary tumor, FTC236 from a c ervical lymph node metastasis, and FTC238 from a lung metastasis. Inva sion was the ability of tumor cells to penetrate 8-mu m pore polycarbo nate membranes coated with Matrigel. Invasion and proliferation were a nalyzed using the MTT assay. For in vivo experiments, athymic nude mic e were sc inoculated with 500,000 cells of FTC133. The animals were tr eated twice daily with octreotide sc (100-300 mu g/kg). RIA studies yi elded dose-dependent high plasma levels of octreotide (3.43-6.5 ng/mL) . Octreotide had a biphasic effect, enhancing growth at low concentrat ions (1-10 nmol/mL) and inhibiting it at high concentrations (100 nmol to 1 mu mol/mL). Octreotide had also a dose-dependent biphasic effect on the invasion of FTC, inhibiting the invasion of all follicular thy roid cancer lines at high concentrations, However, it affected invasio n less than growth. Octreotide (10 nmol/mL) stimulated the invasion of FTC133 by 13%, whereas stimulation was lower in both FTC metastases ( FTC236, 6%; FTC238, 7%; P < 0.01). At higher concentrations (100 nmol to 1 mu mol/mL, octreotide inhibited invasion of FTC133 by 17% (FTC236 , 15%; FTC238, 17%; P < 0.01). During a 3-week treatment period, octre otide had no antiproliferative effect on the growth of FTC133 cells in nude mice. In conclusion, octreotide at low concentrations stimulates and at high concentrations inhibits the growth and invasion of follic ular thyroid cancer cells in culture. However, it has no effect on the growth of FTC cells in animal experiments. Thus, the value of octreot ide as an antitumoral agent in follicular thyroid cancer must be criti cally questioned.