PMID- 31483776
OWN - NLM
STAT- MEDLINE
DCOM- 20200212
LR  - 20200225
IS  - 1643-3750 (Electronic)
IS  - 1234-1010 (Print)
IS  - 1234-1010 (Linking)
VI  - 25
DP  - 2019 Sep 4
TI  - Overexpression of Biglycan is Associated with Resistance to Rapamycin in Human 
      WERI-Rb-1 Retinoblastoma Cells by Inducing the Activation of the 
      Phosphatidylinositol 3-Kinases (PI3K)/Akt/Nuclear Factor kappa B (NF-kappaB) 
      Signaling Pathway.
PG  - 6639-6648
LID - 10.12659/MSM.915075 [doi]
AB  - BACKGROUND Biglycan (BGN) is an extracellular matrix (ECM) protein that regulates 
      the growth of epithelial cells. The mammalian target of rapamycin (mTOR) 
      inhibitor, rapamycin, is a treatment for advanced retinoblastoma. This study 
      aimed to investigate the effects of expression of BGN on the response of human 
      WERI-Rb-1 retinoblastoma cells to rapamycin and to investigate the associated 
      signaling pathways. MATERIAL AND METHODS BGN gene expression was induced in human 
      WERI-Rb-1 retinoblastoma cells, which were incubated with rapamycin at doses of 
      0, 5, 10, 20, 30, and 50 mug/ml. Cells were treated with the PI3K/Akt pathway 
      inhibitor, LY294002. The MTT assay determined the rate of cell inhibition. 
      Real-time polymerase chain reaction (RT-PCR) was performed to measure BGN gene 
      expression using RT(2)-PCR. Western blot detected the protein levels of BGN, 
      p-PI3K, p-Akt, nuclear NF-kappaB, and p65. RESULTS Rapamycin impaired cell 
      growth, induced cell apoptosis, and suppressed the expression levels of p-PI3K, 
      p-Akt, nuclear NF-kappaB, and p65. Overexpression of the BGN gene restored growth 
      potential and inhibited apoptosis and was associated with the activation of the 
      PI3K/Akt-mediated NF-kappaB pathway. In cells that overexpressed BGN, inhibition 
      of the PI3K/Akt pathway by LY294002 increased the sensitivity of human WERI-Rb-1 
      retinoblastoma cells to rapamycin. CONCLUSIONS Overexpression of BGN induced 
      rapamycin resistance in WERI-Rb-1 retinoblastoma cells by activating 
      PI3K/Akt/NF-kappaB signaling.
FAU - Fang, Dong
AU  - Fang D
AD  - Department of Ophthalmology, The Affiliated Hospital of Qingdao University, 
      Qingdao, Shandong, China (mainland).
FAU - Lai, Zhaoguang
AU  - Lai Z
AD  - Department of Ophthalmology, Peoples' Hospital of Guangxi Autonomous Region, 
      Nanning, Guangxi, China (mainland).
FAU - Wang, Yan
AU  - Wang Y
AD  - Department of Ophthalmology, 521 Hospital of Xi'an Weapon Industry, Xi'an, 
      Shaanxi, China (mainland).
LA  - eng
PT  - Journal Article
DEP - 20190904
PL  - United States
TA  - Med Sci Monit
JT  - Medical science monitor : international medical journal of experimental and 
      clinical research
JID - 9609063
RN  - 0 (BGN protein, human)
RN  - 0 (Biglycan)
RN  - 0 (NF-kappa B)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Apoptosis/drug effects
MH  - Biglycan/genetics/*metabolism
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - *Drug Resistance, Neoplasm/drug effects/genetics
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Inhibitory Concentration 50
MH  - NF-kappa B/*metabolism
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Retinoblastoma/genetics/*metabolism/*pathology
MH  - Signal Transduction
MH  - Sirolimus/*pharmacology
PMC - PMC6743380
COIS- Conflict of interest None.
EDAT- 2019/09/05 06:00
MHDA- 2020/02/13 06:00
PMCR- 2019/09/04
CRDT- 2019/09/05 06:00
PHST- 2019/09/05 06:00 [entrez]
PHST- 2019/09/05 06:00 [pubmed]
PHST- 2020/02/13 06:00 [medline]
PHST- 2019/09/04 00:00 [pmc-release]
AID - 915075 [pii]
AID - 10.12659/MSM.915075 [doi]
PST - epublish
SO  - Med Sci Monit. 2019 Sep 4;25:6639-6648. doi: 10.12659/MSM.915075.