β-Carotene synergistically enhances the anti-tumor effect of 5-fluorouracil on esophageal squamous cell carcinoma in vivo and in vitro

Yanting Zhang, Xiangzhan Zhu, Tuanjie Huang, Lei Chen, Yanxia Liu, Qinghua Li, Jishi Song, Shanshan Ma, Kun Zhang, Bo Yang, Fangxia Guan

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Recently, we reported that β-carotene exhibited anticancer activity against human esophageal squamous cell carcinoma cells in vitro. In the present study, we examined a novel therapeutic strategy by combining β-carotene with 5-fluorouracil (5-FU) in human esophageal cancer in vitro and in vivo, and elucidated the underlying mechanisms. We found that the combination of 5-FU and β-carotene displayed greater growth inhibitory effects than did either compound alone in esophageal squamous cell carcinoma (ESCC) cells. In addition, the combination of 5-FU and β-carotene displayed greater tumor growth inhibition in an Eca109 xenograft mouse model than did a single agent with low systemic toxicity. β-Carotene enhanced 5-FU-induced apoptosis. TUNEL staining revealed that the rate of TUNEL-positive cells was markedly increased in tumor tissues after treatment with 5-FU and β-carotene. Western blotting and immunohistochemistry revealed the down-regulation of Bcl-2 and PCNA and the up-regulation of Bax and caspase-3 in tumor tissues. Further studies demonstrated that the combined administration of 5-FU and β-carotene significantly down-regulated the protein levels of Cav-1, p-AKT, p-NF-κB, p-mTOR and p-p70S6K in Eca109 cells more effectively than did 5-FU alone. These data suggested that the combined therapy of 5-FU and β-carotene exerted synergistic antitumor effects in vivo and in vitro and could constitute a novel therapeutic treatment for ESCC.

Original languageEnglish (US)
Pages (from-to)49-58
Number of pages10
JournalToxicology Letters
Volume261
DOIs
StatePublished - Nov 2 2016

Keywords

  • 5-Fluorouracil
  • Apoptosis
  • Esophageal cancer cells
  • Proliferation
  • β-Carotene

ASJC Scopus subject areas

  • Toxicology

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