Combination of SNX-2112 with 5-FU exhibits antagonistic effect in esophageal cancer cells.

[esophageal squamous cell carcinoma]

The low efficacy of single -drug chemotherapy forms the basis for combination therapy in esophageal squamous cell carcinoma . SNX-2112 , a selective heat shock protein 90 (Hsp 90 ) inhibitor , was recently reported as being effective in combination with cisplatin and paclitaxel . In this study , we investigated the effect of SNX-2112 in combination with 5 -fluorouracil (5 -FU ), another first -line anticancer drug , in esophageal cancer . Unexpectedly , tetrazolium assay revealed that the combination of SNX-2112 with 5 -FU exhibited antagonistic effect . Flow cytometry revealed that the SNX-2112 and 5 -FU combination greatly decreased the number of G 2 /M cells compared to SNX-2112 -only treatment in Eca‑109 cells . This effect might be related to the altered mRNA level of cyclin-related genes including cyclin D 1 , Chk 2 and Cdk 4 . Further , 5 -FU attenuated SNX-2112 -induced apoptosis by decreasing poly (ADP-ribose ) polymerase (PARP ) cleavage and inactivating caspase-3 , -8 and -9 . Additionally , 5 -FU suppressed the SNX-2112 -induced decrease of mitochondrial membrane potential . Moreover , 5 -FU partly recovered Hsp 90 client proteins , including Akt , p -Akt , inhibitor of κB kinase (IKK )α , extracellular signal-regulated kinase (ERK )1 /2 , and glycogen synthase kinase (GSK )-3 β , which SNX-2112 had downregulated . Taken together , this is the first report that the combination of SNX-2112 with 5 -FU exhibited antagonistic effect in esophageal cancer cells by affecting growth inhibition , cell cycle , apoptosis , and Hsp 90 client proteins , suggesting that care is required in the clinical application of combined SNX-2112 and 5 -FU .

Diseases
Validation

Diseases presenting "cancer" symptom

achondroplasia

acute rheumatic fever

adrenal incidentaloma

alpha-thalassemia

benign recurrent intrahepatic cholestasis

cadasil

canavan disease

carcinoma of the gallbladder

cholangiocarcinoma

coats disease

congenital adrenal hyperplasia

congenital diaphragmatic hernia

cowden syndrome

cushing syndrome

cutaneous mastocytosis

dedifferentiated liposarcoma

dystrophic epidermolysis bullosa

epidermolysis bullosa simplex

erdheim-chester disease

erythropoietic protoporphyria

esophageal adenocarcinoma

esophageal carcinoma

esophageal squamous cell carcinoma

familial hypocalciuric hypercalcemia

familial mediterranean fever

gm1 gangliosidosis

heparin-induced thrombocytopenia

hereditary cerebral hemorrhage with amyloidosis

hirschsprung disease

hodgkin lymphoma, classical

inclusion body myositis

junctional epidermolysis bullosa

kabuki syndrome

kallmann syndrome

kindler syndrome

lamellar ichthyosis

liposarcoma

locked-in syndrome

lymphangioleiomyomatosis

monosomy 21

neuralgic amyotrophy

oculocutaneous albinism

oligodontia

oral submucous fibrosis

papillon-lefèvre syndrome

pendred syndrome

pleomorphic liposarcoma

primary effusion lymphoma

proteus syndrome

pyomyositis

pyruvate dehydrogenase deficiency

severe combined immunodeficiency

sneddon syndrome

systemic capillary leak syndrome

triple a syndrome

von hippel-lindau disease

waldenström macroglobulinemia

well-differentiated liposarcoma

werner syndrome

wiskott-aldrich syndrome

wolf-hirschhorn syndrome

x-linked adrenoleukodystrophy

This symptom has already been validated