PMID- 28454274
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1792-1074 (Print)
IS  - 1792-1082 (Electronic)
IS  - 1792-1074 (Linking)
VI  - 13
IP  - 3
DP  - 2017 Mar
TI  - Role of endoplasmic reticulum stress on cisplatin resistance in ovarian 
      carcinoma.
PG  - 1437-1443
LID - 10.3892/ol.2017.5580 [doi]
AB  - Endoplasmic reticulum (ER) is an essential site of cellular homeostasis 
      regulation. ER stress (ERS) may induce autophagy in tumor cells that escape from 
      apoptosis. The present study examined the effects and mechanism of ERS on 
      cisplatin (DDP) sensitivity in ovarian carcinoma. SKOV3 tumor cells treated with 
      Saquinavir were subjected to western blot and reverse transcription-quantitative 
      polymerase chain reaction analysis to determine protein and messenger RNA (mRNA) 
      expression levels of mechanistic target of rapamycin (mTOR) and Beclin 1. MTT 
      assay was used to analyze the influence of Saquinavir on DDP resistance in SKOV3 
      cells. Saquinavir induced glucose-regulated protein 78 expression, which is a 
      marker of ERS. Following treatment with various doses of Saquinavir, the 
      sensitivity of ovarian cancer cells to DDP decreased significantly. Protein and 
      mRNA expression levels of mTOR and Beclin 1 in SKOV3 cells were increased when 
      the cells were exposed to Saquinavir or DDP for 24 h. Moreover, mTOR and Beclin 1 
      expression levels were highest in the Saquinavir + DDP group (0.684+/-0.072 and 
      0.6467+/-0.0468, respectively). SKOV3 tumor cells were also exposed to the 
      autophagy inhibitor, 3-methyladenine (3-MA), and different concentrations of 
      Saquinavir. Analysis of half maximal inhibitory concentration (IC(50)) values of 
      DDP after this treatment demonstrated that IC(50) values were significantly 
      decreased compared with Saquinavir alone (P<0.001), suggesting that the 
      sensitivity to DDP was improved in ovarian cancer cells after 3-MA exposure. 
      These findings demonstrated that Saquinavir is able to induce ERS in SKOV3 cells 
      effectively, and ER-induced stress may decrease the sensitivity of DDP in SKOV3 
      cells. Furthermore, ERS may regulate cell autophagy through the mTOR and Beclin 1 
      pathways, leading to a reduction in the sensitivity of DDP in SKOV3 cells. ERS in 
      tumor cells and autophagy may be a potential target to improve the therapeutic 
      effect of chemotherapy and reduce drug resistance in tumors.
FAU - Tian, Jing
AU  - Tian J
AD  - Department of Gynaecology, Tianjin First Central Hospital, Tianjin 300192, P.R. 
      China.
FAU - Liu, Rong
AU  - Liu R
AD  - Department of Gynaecology, Tianjin First Central Hospital, Tianjin 300192, P.R. 
      China.
FAU - Qu, Quanxin
AU  - Qu Q
AD  - Department of Gynaecology, Tianjin First Central Hospital, Tianjin 300192, P.R. 
      China.
LA  - eng
PT  - Journal Article
DEP - 20170110
PL  - Greece
TA  - Oncol Lett
JT  - Oncology letters
JID - 101531236
PMC - PMC5403381
OTO - NOTNLM
OT  - autophagy
OT  - cisplatin
OT  - drug resistance
OT  - endoplasmic reticulum stress
OT  - ovarian carcinoma
EDAT- 2017/04/30 06:00
MHDA- 2017/04/30 06:01
PMCR- 2017/01/10
CRDT- 2017/04/30 06:00
PHST- 2015/06/01 00:00 [received]
PHST- 2016/10/14 00:00 [accepted]
PHST- 2017/04/30 06:00 [entrez]
PHST- 2017/04/30 06:00 [pubmed]
PHST- 2017/04/30 06:01 [medline]
PHST- 2017/01/10 00:00 [pmc-release]
AID - OL-0-0-5580 [pii]
AID - 10.3892/ol.2017.5580 [doi]
PST - ppublish
SO  - Oncol Lett. 2017 Mar;13(3):1437-1443. doi: 10.3892/ol.2017.5580. Epub 2017 Jan 
      10.