Repurposing the Antibiotic Tigecycline to Inhibit Tumor Growth and Hormone Secretion in Somatotroph Pituitary Neuroendocrine Tumors.

Abstract

This investigation employed the rat GH3 somatotroph pituitary neuroendocrine tumor (PitNET) cell line to assess the effects of the antibiotic tigecycline and to preliminarily elucidate its potential molecular mechanisms. GH3 cells were exposed to tigecycline ranging from 6.25 to 100 μM. Cell viability and IC 50 were determined using the CCK-8 assay, and spheroid growth was monitored by measuring diameters. To assess apoptosis, cells were subjected to Annexin V-FITC/PI staining and nuclear morphology observation after DAPI staining. Meanwhile, the cell cycle distribution was profiled via flow cytometry following propidium iodide (PI) staining. The expression of proteins related to the Akt/mTOR pathway, apoptosis, and growth hormone (GH) was evaluated by Western blot. GH secretion was quantified using ELISA. Tigecycline dose and time dependently suppressed GH3 cell proliferation, with IC 50 values of 22.45 μM at 48 h and 9.037 μM at 72 h. It also impeded three-dimensional spheroid growth. Mechanistically, treatment induced G0/G1 phase arrest, significantly suppressed the Akt/mTOR signaling pathway (evidenced by reduced phosphorylation of Akt and mTOR), and activated the intrinsic apoptotic pathway, marked by a rise in the Bax/Bcl-2 ratio and heightened cleaved caspase-3 expression. Additionally, tigecycline significantly attenuated both intracellular synthesis and extracellular secretion of GH. These findings indicate that tigecycline exerts potent antiproliferative and antisecretory effects on GH3 cells, likely through Akt/mTOR pathway inhibition, cell cycle arrest, and apoptosis induction. These results provide an experimental foundation for considering tigecycline as a potential therapeutic agent for GH-secreting PitNET.