Journal
TOXICOLOGY LETTERS
Volume 261, Issue -, Pages 49-58Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2016.08.010
Keywords
beta-Carotene; 5-Fluorouracil; Esophageal cancer cells; Proliferation; Apoptosis
Categories
Funding
- National Natural Science Foundation of China [81471306, U1404313]
- Innovative Research Team (in Science and Technology) of the University of Henan Province [15IRTSTHN022]
- Plan for Scientific Innovation Talent of Henan Province [154200510008]
- Plan for Scientific Innovation Talent of Henan Province
- Key Research Project of Higher Education of Henan Province [15A310028, 15A180022]
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Recently, we reported that beta-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 beta-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 beta-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 beta-carotene displayed greater tumor growth inhibition in an Eca109 xenograft mouse model than did a single agent with low systemic toxicity. b-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 beta-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 beta-carotene significantly down-regulated the protein levels of Cav-1, p-AKT, p-NF-kappa B, 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 beta-carotene exerted synergistic antitumor effects in vivo and in vitro and could constitute a novel therapeutic treatment for ESCC. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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