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.
* Cancer Institute, Southern Medical University, Guangzhou, P.R. China.
Ting
T
Zhu
* Cancer Institute, Southern Medical University, Guangzhou, P.R. China.
Lin-Lin
LL
Li
† Department of Surgery, Xiangya Hospital, Central South University, Changsha, P.R. China.
Guang-Fa
GF
Xiao
* Cancer Institute, Southern Medical University, Guangzhou, P.R. China.
Qi-Zhi
QZ
Luo
* Cancer Institute, Southern Medical University, Guangzhou, P.R. China.
Qiu-Zheng
QZ
Liu
* Cancer Institute, Southern Medical University, Guangzhou, P.R. China.
Kai-Tai
KT
Yao
* Cancer Institute, Southern Medical University, Guangzhou, P.R. China.
Guang-Hui
GH
Xiao
D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001599:Berberine / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D000089042:Coptis chinensis; D018450:Disease Progression; D004317:Doxorubicin / Q000494:pharmacology* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004365:Drugs, Chinese Herbal / Q000737:chemistry; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D008517:Phytotherapy; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D054875:Ubiquitination / Q000187:drug effects
D004365:Drugs, Chinese Herbal; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D001599:Berberine; D004317:Doxorubicin; C107393:Coptidis rhizoma extract
Berberine; Doxorubicin; Lung Cancer; STAT3