Berberine Increases Doxorubicin Sensitivity by Suppressing STAT3 in Lung Cancer

Berberine (BBR), an alkaloid component isolated from Chinese medicinal herb Huang Lian, has aroused broad interests for its antitumor effect in recent years. The signal transducer and activator of transcription 3 (STAT3), plays critical roles in malignant transformation and progression and was found to be constitutively activated in a variety of human cancers. In this study, we show that BBR inhibited cell proliferation, induced apoptosis, and suppressed tumor spheroid formation of lung cancer cell lines. These effects were correlated with BBR-mediated suppression of both phosphorylated and total levels of STAT3 protein. Furthermore, BBR promoted STAT3 degradation by enhancing ubiquitination. Importantly, we demonstrated that BBR was able to inhibit doxorubicin (DOX)-mediated STAT3 activation and sensitize lung cancer cells to the cytotoxic effect of DOX treatment. Given that BBR is widely used in clinic with low toxicity, our results are potentially important for the development of a novel combinatorial therapy with BBR and DOX in the treatment of lung cancer.