PMID- 25744244
OWN - NLM
STAT- MEDLINE
DCOM- 20160315
LR  - 20181113
IS  - 1559-131X (Electronic)
IS  - 1357-0560 (Linking)
VI  - 32
IP  - 4
DP  - 2015 Apr
TI  - Downregulation of ABCE1 via siRNA affects the sensitivity of A549 cells against 
      chemotherapeutic agents.
PG  - 103
LID - 10.1007/s12032-015-0557-3 [doi]
AB  - ATP-binding cassette E1 (ABCE1) is involved in several biological functions in 
      cancer cells such as tumor proliferation, antiapoptotic pathway and 
      chemoresistance mechanism. This work aimed to investigate the alterations in 
      chemosensitivity of A549 lung cancer cells for 5-Fluorouracil (5-FU) and 
      irinotecan by silencing ABCE1 using specific small interfering RNAs (siRNA). The 
      cells were treated with low doses of drugs, alone and also their combinations 
      with ABCE1 siRNA. Cytotoxicity, cell proliferation and apoptosis/necrosis 
      evaluations were performed in order to examine the effects of the combined 
      treatment. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to 
      confirm the downregulation of ABCE1. We also investigated the levels of B cell 
      lymphoma 2 (Bcl-2) and mammalian target of rapamycin (mTOR) after the treatments 
      by RT-PCR. Downregulation of ABCE1 improved the anticancer effects of 5-FU in 
      inducing cell viability/proliferation inhibition and apoptosis/necrosis, whereas 
      interestingly, almost did not change or slightly reduced the anticancer effects 
      of irinotecan. ABCE1 expression significantly decreased by transfecting the cells 
      with ABCE1 siRNA. Moreover, Bcl-2 and mTOR levels changed after the single or 
      combined therapy in parallel with the apoptotic and antiproliferation effect. In 
      conclusion, the simultaneous treatment of lung cancer cells with ABCE1 siRNA and 
      5-FU exhibited synergistic or additive effects; however, ABCE1 siRNA and 
      irinotecan had unexpected antagonistic effects. Our findings demonstrate that the 
      strategy of downregulation of ABCE1 may be included in conventional 5-FU 
      chemotherapy for lung cancer, minimizing the usage of 5-FU at high dosages.
FAU - Kara, Goknur
AU  - Kara G
AD  - Chemistry Department, Biochemistry Division, Hacettepe University, Beytepe, 
      06800, Ankara, Turkey.
FAU - Tuncer, Sema
AU  - Tuncer S
FAU - Turk, Mustafa
AU  - Turk M
FAU - Denkbas, Emir Baki
AU  - Denkbas EB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150306
PL  - United States
TA  - Med Oncol
JT  - Medical oncology (Northwood, London, England)
JID - 9435512
RN  - 0 (ABCE1 protein, human)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
SB  - IM
MH  - ATP-Binding Cassette Transporters/*antagonists & inhibitors/genetics
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis/drug effects
MH  - Cell Proliferation/drug effects
MH  - Drug Resistance, Neoplasm/*genetics
MH  - Gene Expression Regulation, Neoplastic/*drug effects
MH  - Humans
MH  - Lung Neoplasms/*drug therapy/*genetics/pathology
MH  - RNA, Messenger/genetics
MH  - RNA, Small Interfering/*genetics
MH  - Real-Time Polymerase Chain Reaction
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tumor Cells, Cultured
EDAT- 2015/03/07 06:00
MHDA- 2016/03/16 06:00
CRDT- 2015/03/07 06:00
PHST- 2015/02/24 00:00 [received]
PHST- 2015/02/27 00:00 [accepted]
PHST- 2015/03/07 06:00 [entrez]
PHST- 2015/03/07 06:00 [pubmed]
PHST- 2016/03/16 06:00 [medline]
AID - 10.1007/s12032-015-0557-3 [doi]
PST - ppublish
SO  - Med Oncol. 2015 Apr;32(4):103. doi: 10.1007/s12032-015-0557-3. Epub 2015 Mar 6.