PMID- 26530936
OWN - NLM
STAT- MEDLINE
DCOM- 20160923
LR  - 20211203
IS  - 1791-2423 (Electronic)
IS  - 1019-6439 (Print)
IS  - 1019-6439 (Linking)
VI  - 48
IP  - 1
DP  - 2016 Jan
TI  - Apoptosis and antitumor effects induced by the combination of an mTOR inhibitor 
      and an autophagy inhibitor in human osteosarcoma MG63 cells.
PG  - 37-44
LID - 10.3892/ijo.2015.3227 [doi]
AB  - The inhibition of the mammalian target of rapamycin (mTOR) signaling pathway 
      promotes the initiation of autophagy. Although it remains under debate whether 
      chemotherapy-induced autophagy in tumor cells is a protective response or is 
      invoked to promote cell death, recent studies indicate that autophagy is a 
      self-defense mechanism of cancer cells that are subjected to antitumor agents and 
      that blocking autophagy can trigger apoptosis. The aim of this study was to 
      examine the effects of rapamycin, an mTOR inhibitor, on MG63 osteosarcoma cells. 
      We further examined whether the combination of rapamycin and the small molecule 
      inhibitor of autophagy Spautin-1 (specific and potent autophagy inhibitor-1) 
      enhanced the rapamycin-induced apoptosis in MG63 cells. We examined the effects 
      of rapamycin treatment on cell proliferation, phosphorylation of mTOR pathway 
      components, and autophagy by western blot analysis. Furthermore, we examined the 
      effects of rapamycin with or without Spautin-1 on the induction of apoptosis by 
      western blot analysis and immunohistochemical staining. We found that rapamycin 
      inhibited cell proliferation and decreased the phosphorylation of mTOR pathway 
      components in MG63 cells. Rapamycin induced the apoptosis of MG63 cells, and this 
      apoptosis was enhanced by Spautin-1. It was considered that Spautin-1 suppressed 
      the protective mechanism induced by rapamycin in tumor cells and induced 
      apoptosis. Therefore, the combination of an mTOR inhibitor and an autophagy 
      inhibitor may be effective in the treatment of osteosarcoma because it 
      effectively induces the apoptotic pathway.
FAU - Horie, Ryosuke
AU  - Horie R
AD  - Department of Orthopaedic Surgery, Kagawa University School of Medicine, 
      Miki-cho, Kita-gun, Kagawa, Japan.
FAU - Nakamura, Osamu
AU  - Nakamura O
AD  - Department of Orthopaedic Surgery, Kagawa University School of Medicine, 
      Miki-cho, Kita-gun, Kagawa, Japan.
FAU - Yamagami, Yoshiki
AU  - Yamagami Y
AD  - Department of Orthopaedic Surgery, Kagawa University School of Medicine, 
      Miki-cho, Kita-gun, Kagawa, Japan.
FAU - Mori, Masaki
AU  - Mori M
AD  - Department of Orthopaedic Surgery, Kagawa University School of Medicine, 
      Miki-cho, Kita-gun, Kagawa, Japan.
FAU - Nishimura, Hideki
AU  - Nishimura H
AD  - Department of Orthopaedic Surgery, Kagawa University School of Medicine, 
      Miki-cho, Kita-gun, Kagawa, Japan.
FAU - Fukuoka, Natsuko
AU  - Fukuoka N
AD  - Department of Orthopaedic Surgery, Kagawa University School of Medicine, 
      Miki-cho, Kita-gun, Kagawa, Japan.
FAU - Yamamoto, Tetsuji
AU  - Yamamoto T
AD  - Department of Orthopaedic Surgery, Kagawa University School of Medicine, 
      Miki-cho, Kita-gun, Kagawa, Japan.
LA  - eng
PT  - Journal Article
DEP - 20151103
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (Benzylamines)
RN  - 0 (Quinazolines)
RN  - 0 (spautin-1)
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  - Apoptosis/*drug effects
MH  - Autophagy/*drug effects
MH  - Benzylamines/administration & dosage
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Humans
MH  - Osteosarcoma/*drug therapy/genetics/pathology
MH  - Phosphorylation
MH  - Quinazolines/administration & dosage
MH  - Signal Transduction/drug effects
MH  - Sirolimus/*administration & dosage
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/*genetics
PMC - PMC4734606
EDAT- 2015/11/05 06:00
MHDA- 2016/09/24 06:00
PMCR- 2015/11/03
CRDT- 2015/11/05 06:00
PHST- 2015/08/04 00:00 [received]
PHST- 2015/10/12 00:00 [accepted]
PHST- 2015/11/05 06:00 [entrez]
PHST- 2015/11/05 06:00 [pubmed]
PHST- 2016/09/24 06:00 [medline]
PHST- 2015/11/03 00:00 [pmc-release]
AID - ijo-48-01-0037 [pii]
AID - 10.3892/ijo.2015.3227 [doi]
PST - ppublish
SO  - Int J Oncol. 2016 Jan;48(1):37-44. doi: 10.3892/ijo.2015.3227. Epub 2015 Nov 3.