Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.
Institute of Urology, Lanzhou University Second Hospital, Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
Mol Med Rep. 2017 Dec;16(6):8563-8571. doi: 10.3892/mmr.2017.7665. Epub 2017 Sep 29.
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.
果糖-1,6-二磷酸酶-1（FBP1）是一种在各种组织中表达的糖异生限速酶，在各种癌症的发生中起着重要作用。为了评估 FBP1 表达与宫颈癌发生和化疗耐药的关系，本研究分析了 140 例接受根治性手术后辅助同步放化疗的宫颈鳞癌（CSCC）患者的石蜡包埋肿瘤组织中 FBP1 蛋白的表达。通过免疫组织化学方法检测 FBP1 蛋白在肿瘤组织中的表达，发现 50%的病例 FBP1 表达较低，与总生存期较短相关（P=0.011）。此外，与宫颈正常组织相比，肿瘤组织中 FBP1 mRNA 水平下调。在与肿瘤相关的预后因素中，FBP1 表达缺失（卡方检验，P=0.025）与宫颈癌患者的肿瘤复发和更大的肿瘤分期显著相关（2 检验，P<0.0001）。在原代肿瘤细胞的 3-（4,5）-二甲基噻唑（-z-y1）-3,5-二苯基四唑溴盐（MTT）测定中，顺铂、卡铂、奈达铂和奥沙利铂的体外抑制率中位数分别为 62%、47%、58%和 52%。尽管 FBP1 表达与原代肿瘤细胞的体外肿瘤抑制率之间没有显著关联，但 FBP1 的过表达显著抑制了宫颈癌的发生，并恢复了宫颈癌细胞系 HeLa 和 CaSki 对顺铂的化疗敏感性。总之，FBP1 水平的降低可能可作为宫颈癌患者预后不良的预测因子，但具体机制仍需进一步研究。
