Rare Diseases Symptoms Automatic Extraction

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 (Hsp90) 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 G2/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 D1, Chk2 and Cdk4. 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 Hsp90 client proteins, including Akt, p-Akt, inhibitor of κB kinase (IKK)α, extracellular signal-regulated kinase (ERK)1/2, and glycogen synthase kinase (GSK)-3β, 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 Hsp90 client proteins, suggesting that care is required in the clinical application of combined SNX-2112 and 5-FU.

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