PMID- 25310356
OWN - NLM
STAT- MEDLINE
DCOM- 20150619
LR  - 20211203
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Linking)
VI  - 10
IP  - 6
DP  - 2014 Dec
TI  - Berberine sensitizes rapamycin‑mediated human hepatoma cell death in vitro.
PG  - 3132-8
LID - 10.3892/mmr.2014.2608 [doi]
AB  - Rapamycin is clinically used as an immunosuppressant. Increasing evidence 
      suggests that rapamycin has an important inhibitory role in the development and 
      progression of different types of cancer and that it is a promising candidate for 
      cancer chemotherapy. Berberine is an isoquinoline alkaloid isolated from 
      medicinal plant species, which has been used in traditional Chinese medicine with 
      no significant side effects. Recent research has demonstrated that berberine has 
      anticancer activity against various types of cancer, mediated through the 
      suppression of mammalian target of rapamycin (mTOR). The present study aimed to 
      investigate the in vitro synergistic anticancer effect of combined treatment of 
      rapamycin at various concentrations (0, 10, 50, 100 and 200 nM) and berberine 
      (62.5 microM) in SMMC7721 and HepG2 hepatocellular carcinoma (HCC) cell lines, and 
      the potential underlying molecular mechanism. The combined use of rapamycin and 
      berberine was found to have a synergistic cytotoxic effect, with berberine 
      observed to maintain the cyotoxic effect of rapamycin on HCC cells at a lower 
      rapamycin concentration. Moreover, the cells treated with the combination of the 
      two agents exhibited significantly decreased protein levels of phosphorylated 
      (p)‑p70S6 kinase 1 (Thr389), the downstream effector of mTOR, compared with the 
      cells treated with rapamycin or berberine alone. Furthermore, overexpression of 
      cluster of differentiation (CD) 147, a transmembrance glycoprotein associated 
      with the anticancer effects of berberine, was found to upregulate p‑mTOR 
      expression and inhibit cell death in SMMC7721 cells co‑treated with rapamycin and 
      berberine. In conclusion, the findings of the present study suggest that the 
      combined use of rapamycin and berberine may improve HCC therapy through 
      synergistically inhibiting the mTOR signaling pathway, which is at least in part, 
      mediated through CD147.
FAU - Guo, Na
AU  - Guo N
AD  - Laboratory of Cell Biology and Translational Medicine, Institute of Basic Medical 
      Science, X'ian Medical University, Xi'an, Shaanxi 710021, P.R. China.
FAU - Yan, Aili
AU  - Yan A
AD  - Laboratory of Cell Biology and Translational Medicine, Institute of Basic Medical 
      Science, X'ian Medical University, Xi'an, Shaanxi 710021, P.R. China.
FAU - Gao, Xingchun
AU  - Gao X
AD  - Laboratory of Cell Biology and Translational Medicine, Institute of Basic Medical 
      Science, X'ian Medical University, Xi'an, Shaanxi 710021, P.R. China.
FAU - Chen, Yanke
AU  - Chen Y
AD  - Department of Cell Biology and Genetics, College of Medicine, Xi'an Jiaotong 
      University, Xi'an, Shaanxi 710032, P.R. China.
FAU - He, Xinying
AU  - He X
AD  - Laboratory of Cell Biology and Translational Medicine, Institute of Basic Medical 
      Science, X'ian Medical University, Xi'an, Shaanxi 710021, P.R. China.
FAU - Hu, Zhifang
AU  - Hu Z
AD  - Laboratory of Cell Biology and Translational Medicine, Institute of Basic Medical 
      Science, X'ian Medical University, Xi'an, Shaanxi 710021, P.R. China.
FAU - Mi, Man
AU  - Mi M
AD  - Laboratory of Cell Biology and Translational Medicine, Institute of Basic Medical 
      Science, X'ian Medical University, Xi'an, Shaanxi 710021, P.R. China.
FAU - Tang, Xu
AU  - Tang X
AD  - Department of Pathology, Sichuan College of Traditional Chinese Medicine, 
      Mianyang, Sichuan 721000, P.R. China.
FAU - Gou, Xingchun
AU  - Gou X
AD  - Laboratory of Cell Biology and Translational Medicine, Institute of Basic Medical 
      Science, X'ian Medical University, Xi'an, Shaanxi 710021, P.R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141008
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0I8Y3P32UF (Berberine)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Berberine/*pharmacology
MH  - Carcinoma, Hepatocellular/*drug therapy/metabolism
MH  - Cell Death/*drug effects
MH  - Cell Line, Tumor
MH  - Drug Synergism
MH  - Hep G2 Cells
MH  - Humans
MH  - Liver Neoplasms/*drug therapy/metabolism
MH  - Signal Transduction/drug effects
MH  - Sirolimus/*pharmacology
MH  - TOR Serine-Threonine Kinases/metabolism
EDAT- 2014/10/14 06:00
MHDA- 2015/06/20 06:00
CRDT- 2014/10/14 06:00
PHST- 2013/09/18 00:00 [received]
PHST- 2014/04/24 00:00 [accepted]
PHST- 2014/10/14 06:00 [entrez]
PHST- 2014/10/14 06:00 [pubmed]
PHST- 2015/06/20 06:00 [medline]
AID - 10.3892/mmr.2014.2608 [doi]
PST - ppublish
SO  - Mol Med Rep. 2014 Dec;10(6):3132-8. doi: 10.3892/mmr.2014.2608. Epub 2014 Oct 8.