HCFU inhibits cervical cancer cells growth and metastasis by inactivating Wnt/β-catenin pathway

J Cell Biochem. 2017 Dec 12. doi: 10.1002/jcb.26570. Online ahead of print.

Abstract

Background: 1-hexylcarbamoyl-5-fluorouracil (HCFU), also known as carmofur, is an effective chemotherapeutic agent applied to several cancers. This study was aimed to explore the functional effects of HCFU on cervical cancer cells and tried to uncover its possible mechanism.

Methods: Two immortalized cervical cancer cell lines (HeLa and Caski) and primary cervical cancer cells prepared from two cervical cancer patients were used in this study. Cell viability, apoptosis, colony formation, migration, invasion, and the expressions of cell growth- and metastasis-associated factors were respectively assessed following 0-1 µg/mL of HCFU treatment for 0-48 h. Besides, the expressions of main factors in Wnt/β-catenin signaling pathway were detected following HCFU administration.

Results: As a result, HCFU significantly suppressed HeLa and Caski cells viability but promoted apoptosis, both in time- and dose-dependent manner (P < 0.05 or P < 0.01). Besides, HCFU reduced these two cell lines colony formation capacity, migration and invasion (P < 0.05, P < 0.01 or P < 0.001). In primary cervical cancer cells, cell viability was reduced (P < 0.05 or P < 0.01), the expressions of Cyclin D1, MMP2 and MMP9 were down-regulated, while the expression of E-Cadherin was up-regulated after HCFU treatment. Further, HCFU down-regulated the expressions of intranuclear β-catenin, c-Myc, and TCF-1, but has no impacts on intracytoplasmic β-catenin expression in HeLa cells and primary cervical cancer cells.

Conclusion: This study demonstrated an anti-growth and anti-metastasis role of HCFU in cervical cancer cells. HCFU suppressed cervical cancer possibly via blocking Wnt/β-catenin signaling pathway. This article is protected by copyright. All rights reserved.

Keywords: 1-hexylcarbamoyl-5-fluorouracil (HCFU); Wnt/β-catenin pathway; cervical cancer; metastasis; proliferation.