PMID- 29397960
OWN - NLM
STAT- MEDLINE
DCOM- 20190208
LR  - 20211204
IS  - 1618-0372 (Electronic)
IS  - 0065-1281 (Linking)
VI  - 120
IP  - 2
DP  - 2018 Feb
TI  - Synergistic anti-proliferative effects of mTOR and MEK inhibitors in high-grade 
      chondrosarcoma cell line OUMS-27.
PG  - 142-150
LID - S0065-1281(17)30248-9 [pii]
LID - 10.1016/j.acthis.2018.01.002 [doi]
AB  - Chondrosarcoma is a malignant bone tumor that produces cartilaginous neoplastic 
      tissue. Owing to the absence of an effective adjuvant therapy, high-grade 
      chondrosarcoma has a poor prognosis. Therefore, it is important to develop an 
      effective adjuvant therapy to prevent the recurrence and metastasis. Mammalian 
      target of rapamycin (mTOR), a central regulator of cell growth, metabolism, 
      proliferation, and survival, is considered an important target for anticancer 
      drug development. The mitogen activated protein kinase (MAPK) pathway is another 
      highly implicated cellular pathway in cancer and is thought to have compensatory 
      effects in response to the inhibition of the phosphatidylinositol-3-kinase 
      (PI3K)/Akt/mTOR signaling pathway. We investigated the mechanism of 
      anti-proliferative effect of the mTOR inhibitor rapamycin and MAPK/ERK (MEK) 
      inhibitor PD 0325901, and the combined effect of rapamycin and PD 0325901 on 
      human chondrosarcoma cell line (OUMS-27). Combination therapy with rapamycin and 
      PD 0325901 showed a stronger anti-proliferative effect on OUMS-27 cells than 
      rapamycin monotherapy. We confirmed that the dual inhibition of the PI3K/Akt/mTOR 
      and RAF/MEK/ERK signaling pathways had synergistic anti-proliferative effects in 
      OUMS-27. Our results suggest that combination therapy of mTOR and MEK inhibitor 
      could be an effective therapeutic approach against chondrosarcoma.
CI  - Copyright (c) 2018 Elsevier GmbH. All rights reserved.
FAU - Fukumoto, Singo
AU  - Fukumoto S
AD  - Department of Orthopedics, Osaka Medical College, Takatsuki, Osaka, Japan.
FAU - Kanbara, Kiyoto
AU  - Kanbara K
AD  - Department of Orthopedics, Osaka Medical College, Takatsuki, Osaka, Japan. 
      Electronic address: an2007@osaka-med.ac.jp.
FAU - Neo, Masashi
AU  - Neo M
AD  - Department of Orthopedics, Osaka Medical College, Takatsuki, Osaka, Japan.
LA  - eng
PT  - Journal Article
DEP - 20180203
PL  - Germany
TA  - Acta Histochem
JT  - Acta histochemica
JID - 0370320
RN  - 0 (Antineoplastic Agents)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/classification/*therapeutic use
MH  - Blotting, Western
MH  - Cell Cycle/drug effects
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Cell Survival
MH  - *Drug Synergism
MH  - Flow Cytometry
MH  - Humans
MH  - MAP Kinase Signaling System/drug effects
MH  - Mitogen-Activated Protein Kinases/*antagonists & inhibitors
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors
OTO - NOTNLM
OT  - Chondrosarcoma
OT  - Dual inhibitor
OT  - MEK inhibitor
OT  - OUMS-27
OT  - PD 0325901
OT  - Rapamycin
OT  - Synergistic effect
OT  - mTOR inhibitor
EDAT- 2018/02/06 06:00
MHDA- 2019/02/09 06:00
CRDT- 2018/02/06 06:00
PHST- 2017/08/11 00:00 [received]
PHST- 2018/01/08 00:00 [revised]
PHST- 2018/01/09 00:00 [accepted]
PHST- 2018/02/06 06:00 [pubmed]
PHST- 2019/02/09 06:00 [medline]
PHST- 2018/02/06 06:00 [entrez]
AID - S0065-1281(17)30248-9 [pii]
AID - 10.1016/j.acthis.2018.01.002 [doi]
PST - ppublish
SO  - Acta Histochem. 2018 Feb;120(2):142-150. doi: 10.1016/j.acthis.2018.01.002. Epub 
      2018 Feb 3.