Inhibition of autophagy enhances the antitumour activity of tigecycline in multiple myeloma.

Inhibition of autophagy enhances the antitumour activity of tigecycline in multiple myeloma.
J Cell Mol Med. 2018 Sep 24;:
Authors: Ma R, Zhang Y, Wang W, Wu J, Yang Q, Xu W, Jiang S, Han Y, Yu K, Zhang S
Abstract
Accumulating evidence shows that tigecycline, a first-in-class glycylcycline, has potential antitumour properties. Here, we found that tigecycline dramatically inhibited the proliferation of multiple myeloma (MM) cell lines RPMI-8226, NCI-H929 and U266 in a dose and time-dependent manner. Meanwhile, tigecycline also potently impaired the colony formation of these three cell lines. Mechanism analysis found that tigecycline led to cell cycle arrest at G0/G1 with down-regulation of p21, CDK2 and cyclin D1, rather than induced apoptosis, in MM cells. Importantly, we found that tigecycline induced autophagy and an autophagy inhibitor bafilomycin A1 further amplified the tigecycline-induced cytotoxicity, suggesting that autophagy plays a cytoprotective role in tigecycline-treated MM cells. Mechanisms modulating autophagy found that tigecycline enhanced the phosphorylation of AMPK, but did not decrease the phosphorylation of Akt, to inhibit the phosphorylation of mTOR and its two downstream effectors p70S6K1 and 4E-BP1. Tigecycline effectively inhibited tumour growth in the xenograft tumour model of RPMI-8226 cells. Autophagy also occurred in tigecycline-treated tumour xenograft, and autophagy inhibitor chloroquine and tigecycline...

Source: J Cell Mol Med - September 24, 2018 Category: Molecular Biology Authors: Ma R, Zhang Y, Wang W, Wu J, Yang Q, Xu W, Jiang S, Han Y, Yu K, Zhang S Tags: J Cell Mol Med Source Type: research