Octreotide restricts GH-secreting tumor growth by inhibiting mTOR

Somatostatin analogue (SSA) treatment in patients with acromegaly results in tumor shrinkage in ˜40% of the cases. However, the mechanisms behind SSA induced tumor shrinkage are not clear. Histological examination of excised tumors from patients treated with SSA did not reveal apoptotic features, suggesting that most probably mechanisms other than apoptosis account for the inhibitory action of SSA on GH-secreting tumor growth. In contrast changes in tumor cell size were observed in SSA-responsive tumors. The mammalian target of rapamycin (mTOR) pathway is an evolutionary conserved primary regulator of cell growth. Therefore it is possible that SSA decreases cell size by affecting mTOR. Indeed treating the rat GH-secreting cell line GH3 with the SSA octreotide, decreased phospho-mTOR-Ser2448 and mTOR-Ser24811 levels. Octreotide treatment also decreased phospho-p70/S6K-Thr389 levels, which is the primary target downstreams to mTOR. The effect of octreotide was pertussis toxin sensitive indicating involvement of G protein Gi. mTOR phosphorylation is regulated by Akt. In a previous study we have shown that octreotide decreases Akt activation. It is therefore possible that octreotide decreases mTOR phosphorylation by inhibiting Akt. These preliminary data suggest a mechanism through which SSA treatment restricts GH-secreting tumor growth.