PMID- 26807315
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20160125
LR  - 20201001
IS  - 2156-6976 (Print)
IS  - 2156-6976 (Electronic)
IS  - 2156-6976 (Linking)
VI  - 5
IP  - 11
DP  - 2015
TI  - Targeting oncogenic KRAS in non-small cell lung cancer cells by phenformin 
      inhibits growth and angiogenesis.
PG  - 3339-49
AB  - Tumors require a vascular supply to grow and can achieve this via the expression 
      of pro-angiogenic growth factors. Many potential oncogenic mutations have been 
      identified in tumor angiogenesis. Somatic mutations in the small GTPase KRAS are 
      the most common activating lesions found in human cancer, and are generally 
      associated with poor response to standard therapies. Biguanides, such as the 
      diabetes therapeutics metformin and phenformin, have demonstrated anti-tumor 
      activity both in vitro and in vivo. The extracellular regulated protein kinases 
      (ERK) signaling is known to be a major cellular target of biguanides. Based on 
      KRAS activates several down-stream effectors leading to the stimulation of the 
      RAF/mitogen-activated protein kinase/extracellular signal-regulated kinase 
      (RAF/MEK/ERK) and phosphatidylinositol-3-kinase (PI3K) pathways, we investigated 
      the anti-tumor effects of biguanides on the proliferation of KRAS-mutated tumor 
      cells in vitro and on KRAS-driven tumor growth in vivo. In cancer cells harboring 
      oncogenic KRAS, phenformin switches off the ERK pathway and inhibit the 
      expression of pro-angiogenic molecules. In tumor xenografts harboring the KRAS 
      mutation, phenformin extensively modifies the tumor growth causing abrogation of 
      angiogenesis. These results strongly suggest that significant therapeutic 
      advantage may be achieved by phenformin anti-angiogenesis for the treatment of 
      tumor.
FAU - Wang, Zhi Dong
AU  - Wang ZD
AD  - Department of Oncology, Eighth Hospital of Changsha No. 22 Xingsha Avenue, 
      Changsha 410100, Hunan Province, China.
FAU - Wei, Sheng Quan
AU  - Wei SQ
AD  - Department of Respiration, Shanxi Baoji People's Hospital No. 24 Xinhua Lane, 
      Jinger Road, Baoji 721000, Shanxi Province, China.
FAU - Wang, Qin Yi
AU  - Wang QY
AD  - Department of Chemical Engineering, University of Missouri-Columbia MO 
      65211-2200, USA.
LA  - eng
PT  - Journal Article
DEP - 20151015
PL  - United States
TA  - Am J Cancer Res
JT  - American journal of cancer research
JID - 101549944
PMC - PMC4697681
OTO - NOTNLM
OT  - KRAS
OT  - NSCLC
OT  - angiogenesis
OT  - phenformin
EDAT- 2016/01/26 06:00
MHDA- 2016/01/26 06:01
PMCR- 2015/10/15
CRDT- 2016/01/26 06:00
PHST- 2015/08/13 00:00 [received]
PHST- 2015/08/22 00:00 [accepted]
PHST- 2016/01/26 06:00 [entrez]
PHST- 2016/01/26 06:00 [pubmed]
PHST- 2016/01/26 06:01 [medline]
PHST- 2015/10/15 00:00 [pmc-release]
PST - epublish
SO  - Am J Cancer Res. 2015 Oct 15;5(11):3339-49. eCollection 2015.