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 journalArticle

8 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Carotenoids
Fluorouracil
Tumors
Neoplasms
Cells
In Situ Nick-End Labeling
Tissue
70-kDa Ribosomal Protein S6 Kinases
Therapeutics
In Vitro Techniques
Esophageal Squamous Cell Carcinoma
Epithelial Cells
Proliferating Cell Nuclear Antigen
Esophageal Neoplasms
Growth
Heterografts
Human Activities
Caspase 3
Toxicity
Up-Regulation

Keywords

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

ASJC Scopus subject areas

  • Toxicology

Cite this

β-Carotene synergistically enhances the anti-tumor effect of 5-fluorouracil on esophageal squamous cell carcinoma in vivo and in vitro. / Zhang, Yanting; Zhu, Xiangzhan; Huang, Tuanjie; Chen, Lei; Liu, Yanxia; Li, Qinghua; Song, Jishi; Ma, Shanshan; Zhang, Kun; Yang, Bo; Guan, Fangxia.

In: Toxicology Letters, Vol. 261, 02.11.2016, p. 49-58.

Research output: Contribution to journalArticle

Zhang, Yanting ; Zhu, Xiangzhan ; Huang, Tuanjie ; Chen, Lei ; Liu, Yanxia ; Li, Qinghua ; Song, Jishi ; Ma, Shanshan ; Zhang, Kun ; Yang, Bo ; Guan, Fangxia. / β-Carotene synergistically enhances the anti-tumor effect of 5-fluorouracil on esophageal squamous cell carcinoma in vivo and in vitro. In: Toxicology Letters. 2016 ; Vol. 261. pp. 49-58.
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AU - Chen, Lei

AU - Liu, Yanxia

AU - Li, Qinghua

AU - Song, Jishi

AU - Ma, Shanshan

AU - Zhang, Kun

AU - Yang, Bo

AU - Guan, Fangxia

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N2 - 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.

AB - 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.

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