Ambroxol enhances anti-cancer effect of microtubule-stabilizing drug to lung carcinoma through blocking autophagic flux in lysosome-dependent way.

ABSTRACT: Lung carcinoma has become a more and more serious health problem as platinum-based chemotherapy remains a limited benefit. Accumulating evidences indicate that autophagy plays a significant role in decreased curative effect and chemotherapy failure. Inhibition of autophagy can potentiate anti-proliferation effect and contribute to tumor regression in lung carcinoma. Here, we showed that the expectorant drug ambroxol (Ax) promoted autophagosomes accumulation by blocking late-stage autophagic flux in lung carcinoma cells. Furthermore, Ax treatment caused alkalization of lysosome and impaired lysosomal degradation capacity, which contributed to decreased autophagosomes-lysosomes fusion and interrupted normal cargo degradation. Ax potentiated cell-killing sensitivity of paclitaxel (PTX) and doc

SUBMITTER: Zhang X 

PROVIDER: S-EPMC5752683 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature