Fructose‑1,6‑bisphosphatase‑1 decrease may promote carcinogenesis and chemoresistance in cervical cancer

Mol Med Rep. 2017 Dec;16(6):8563-8571. doi: 10.3892/mmr.2017.7665. Epub 2017 Sep 29.

Abstract

Fructose-1,6-bisphosphatase-1 (FBP1), a gluconeogenesis rate-limiting enzyme expressed in various tissues, is important in the carcinogenesis of various cancers. To evaluate the association of FBP1 expression and carcinogenesis and chemoresistance in cervical cancer, the present study analyzed 140 patients of squamous cell carcinoma of cervical cancer (CSCC) who had adjuvant concurrent chemoradiation therapy following radical surgery. By detecting FBP1 protein expression in paraffin‑embedded tumor tissues through immunohistochemistry, it was observed that 50% of the cases had a low expression of FBP1, which was associated with a shorter overall survival time (P=0.011). In addition, FBP1 mRNA level was downregulated in tumor tissues, compared with cervical normal tissues. Among the tumor‑associated prognostic factors, loss of FBP1 expression (χ2‑test, P=0.025) was significantly associated with the tumor recurrence and greater tumor stage of cervical cancer patients (2‑test, P<0.0001). In 3‑(4,5)‑dimethylthiahiazo(‑z‑y1)-3,5-diphenytetrazoliumromide (MTT) assay of primary tumor cells, the median in vitro inhibition rate of cisplatin, carboplatin, nedaplatin, and oxaliplatin was 62, 47, 58 and 52%, respectively. Although there was no significant association between FBP1 expression and in vitro tumor inhibition rates of primary tumor cells, overexpression of FBP1 markedly suppressed carcinogenesis and restored the chemosensitivity to cisplatin in cervical cancer cell lines of HeLa and CaSki. Overall, decreased levels of FBP1 may be used as a predictor for poor prognosis of cervical cancer patients, however the mechanism requires further investigation.

MeSH terms

  • Adult
  • Carcinogenesis / drug effects
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology*
  • Cell Line, Tumor
  • Cisplatin / pharmacology
  • Cisplatin / therapeutic use
  • Drug Resistance, Neoplasm* / drug effects
  • Female
  • Fructose-Bisphosphatase / metabolism*
  • Humans
  • Middle Aged
  • Neoplasm Recurrence, Local / pathology
  • Prognosis
  • Proportional Hazards Models
  • Tumor Stem Cell Assay
  • Uterine Cervical Neoplasms / drug therapy
  • Uterine Cervical Neoplasms / enzymology*
  • Uterine Cervical Neoplasms / pathology*

Substances

  • Fructose-Bisphosphatase
  • Cisplatin