PMID- 25270341
OWN - NLM
STAT- MEDLINE
DCOM- 20150619
LR  - 20141022
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Linking)
VI  - 10
IP  - 6
DP  - 2014 Dec
TI  - Inhibition of the p38 MAPK pathway sensitizes human gastric cells to doxorubicin 
      treatment in vitro and in vivo.
PG  - 3275-81
LID - 10.3892/mmr.2014.2598 [doi]
AB  - Gastric cancer is the second most common cause of cancer-related deaths 
      worldwide. Doxorubicin-based chemotherapeutic regimes have been the mainstay of 
      systemic treatment for disseminated gastric cancer for numerous years. However, 
      the ef fi cacy of doxorubicin is severely limited due to chemoresistance. 
      Chemoresistance is a tightly regulated process, under the control of numerous 
      signal transduction pathways. Amongst these, the mitogen-activated protein kinase 
      (MAPK) pathway has received much attention. This study assessed whether the p38 
      MAPK pathway is involved in doxorubicin resistance in gastric cancer cells. 
      Doxorubicin alone or combined with the p38 MAPK pathway inhibitor SB203580 was 
      used to treat gastric cancer cells (SGC7901 and BGC823 lines). The effect of 
      doxorubicin on the growth and apoptosis of gastric cancer cells in the presence 
      or absence of SB203580 was investigated by western blot analysis, 
      3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Hoechst 
      staining, Annexin V-FITC/propidium iodide staining followed by  fl ow cytometry 
      analysis, and the terminal deoxynucleotidyl transferase-mediated dUTP nick end 
      labeling (TUNEL) assay. Next, the effects of doxorubicin and SB203580, on the 
      sensitivity of BGC-823 cells were assessed in a tumor xenograft model. The 
      results showed that the p38 MAPK inhibitor significantly increases gastric cancer 
      cell sensitivity to doxorubicin. Doxorubicin in combination with SB203580 
      significantly reduced cell viability (P<0.01) and increased cell death (P<0.01), 
      which may be associated with the inactivation of the p38 MAPK signaling pathway, 
      followed by the induced expression of the pro-apoptotic protein Bax and a 
      concomitant decrease in Bcl-2 expression. These findings suggest that p38 MAPK is 
      involved in gastric cancer cell survival, and that the inhibition of p38 MAPK 
      signaling can reduce the tolerance of gastric cancer cells to doxorubicin 
      treatment.
FAU - Tan, Wei
AU  - Tan W
AD  - Department of Gastroenterology, Wuhan University, Renmin Hospital, Wuhan, Hubei 
      430060, P.R. China.
FAU - Yu, Hong-Gang
AU  - Yu HG
AD  - Institute for Gastroenterology and Hepatology, Wuhan University Medical School, 
      Wuhan, Hubei 430060, P.R. China.
FAU - Luo, He-Sheng
AU  - Luo HS
AD  - Institute for Gastroenterology and Hepatology, Wuhan University Medical School, 
      Wuhan, Hubei 430060, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20140925
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (BAX protein, human)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 80168379AG (Doxorubicin)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Apoptosis/drug effects
MH  - Cell Death/drug effects
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Doxorubicin/*pharmacology
MH  - Humans
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Signal Transduction/*drug effects
MH  - Stomach Neoplasms/*drug therapy/metabolism
MH  - bcl-2-Associated X Protein/metabolism
MH  - p38 Mitogen-Activated Protein Kinases/*metabolism
EDAT- 2014/10/02 06:00
MHDA- 2015/06/20 06:00
CRDT- 2014/10/02 06:00
PHST- 2013/10/23 00:00 [received]
PHST- 2014/05/15 00:00 [accepted]
PHST- 2014/10/02 06:00 [entrez]
PHST- 2014/10/02 06:00 [pubmed]
PHST- 2015/06/20 06:00 [medline]
AID - 10.3892/mmr.2014.2598 [doi]
PST - ppublish
SO  - Mol Med Rep. 2014 Dec;10(6):3275-81. doi: 10.3892/mmr.2014.2598. Epub 2014 Sep 
      25.