Research Article

Gene Network Analysis of Glucose Linked Signaling Pathways and Their Role in Human Hepatocellular Carcinoma Cell Growth and Survival in HuH7 and HepG2 Cell Lines

Table 3

Pathways tested on real-time experiments.

PathwayDrug activator (A)/inhibitor (I)Highest dose
tested
Time of
significant effect
HepG2HuH7
EffectIC50 (M)EffectIC50 (M)

AMPKAICAR (A)2 mM24 hr 3 10−31.1 10−3
Compound C (I)40 M24 hrNo effect3.3 10−5
JAK1Butein (I)50 M24 hr2 10−5Nd
JNKSP600125 (I)100 M24 hr1.8 10−52.2 10−5
LKB1Oligomycin (A)2 mM48 hr3 10−72.5 10−7
Metformin (A)10 mM24 hr7 10−68 10−4
Mek1/2U0126 (I)250 M1 hr1.1 10−5Nd
mTORRapamycin (I)200 nM48 hrNo effectNo effect
Mitochondrial apoptosisGSH (A)10 M24 hr 10−61.3 10−4
NFκB p65Wedelolactone (I)10 M24 hr0.8 10−510−5
NOXVAS2780 (I)50 M1 hr5 10−51.8 10−5
P38MAPKSD169 (I)300 M24 hr +9.4 10−5No effect
P42/44A6355 (I)90 M1 hr
PKAKT5720 (I)20 M48 hr +1.1 10−4 +Nd
PKCP3115 (I)50 M1 hr5 10−6Nd
Pi3KLY294002 (I)50 M48 hr3.3 10−53 10−5
PPARAGW6471 (I)1 mM1 hr5.7 10−44 10−4

AMPK, 5′-AMP-activated protein kinase; AICAR: 5-aminoimidazole-4-carboxamide ribonucléotide; GSH: reduced glutathione; JAK1: Janus kinase 1; JNK: Jun-NH2 kinase; LKB1: serine/threonine kinase 11; NFκBp65: nuclear factor kappa B p65 subunit; NOX: NADPH oxidases; P38MAPK: P38 mitogen-activated kinase; Pi3K: Pi3 kinase; PKA: protein kinase AMPc-dependant; PKC, protein kinase C; and PPARA, peroxisome-proliferator activated receptor alpha.