A SOMATOSTATIN ANALOG INHIBITS MAP KINASE ACTIVATION AND CELL-PROLIFERATION IN HUMAN NEUROBLASTOMA AND IN HUMAN SMALL-CELL LUNG-CARCINOMA CELL-LINES

Somatostatin possesses antisecretory and antiproliferative activity on some human tumors, We herein report that, in a human neuroblastoma ce ll line, the somatostatin analogue BIM 23014 inhibited mitogen-activat ed protein (MAP) kinase activity stimulated by either insulin-like gro wth factor-1, whose receptor bears a tyrosine kinase, or carbachol, wh ich acts at a G-protein coupled receptor, In a human small cell lung c arcinoma line BIM inhibited serum-stimulated MAP kinase activation, Th ese inhibitory actions occur in a dose range quite similar to that obs erved for suppression of proliferation induced by the analogue in the same cell lines, The decrease in cAMP elicited by the analogue in the two cell lines is not responsible for its inhibitory action on MAP kin ase and cell growth, Moreover, the analogue did not modify intracellul ar [Ca2+] acid pH. An involvement of a phosphatase activity is suggest ed.