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2017 ; 8
(36
): 60342-60357
Nephropedia Template TP
gab.com Text
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Phenformin inhibits growth and epithelial-mesenchymal transition of
ErbB2-overexpressing breast cancer cells through targeting the IGF1R pathway
#MMPMID28947975
Guo Z
; Zhao M
; Howard EW
; Zhao Q
; Parris AB
; Ma Z
; Yang X
Oncotarget
2017[Sep]; 8
(36
): 60342-60357
PMID28947975
show ga
Reports suggest that metformin, a popular anti-diabetes drug, prevents breast
cancer through various systemic effects, including insulin-like growth factor
receptor (IGFR) regulation. Although the anti-cancer properties of metformin have
been well-studied, reports on a more bioavailable/potent biguanide, phenformin,
remain sparse. Phenformin exerts similar functional activity to metformin and has
been reported to impede mammary carcinogenesis in rats. Since the effects of
phenformin on specific breast cancer subtypes have not been fully explored, we
used ErbB2-overexpressing breast cancer cell and animal models to test the
anti-cancer potential of phenformin. We report that phenformin (25-75 ?M)
decreased cell proliferation and impaired cell cycle progression in SKBR3 and
78617 breast cancer cells. Reduced tumor size after phenformin treatment (30
mg/kg/day) was demonstrated in an MMTV-ErbB2 transgenic mouse syngeneic tumor
model. Phenformin also blocked epithelial-mesenchymal transition, decreased the
invasive phenotype, and suppressed receptor tyrosine kinase signaling, including
insulin receptor substrate 1 and IGF1R, in ErbB2-overexpressing breast cancer
cells and mouse mammary tumor-derived tissues. Moreover, phenformin suppressed
IGF1-stimulated proliferation, receptor tyrosine kinase signaling, and
epithelial-mesenchymal transition markers in vitro. Together, our study
implicates phenformin-mediated IGF1/IGF1R regulation as a potential anti-cancer
mechanism and supports the development of phenformin and other biguanides as
breast cancer therapeutics.