title: β-Carotene synergistically enhances the anti-tumor effect of 5-fluorouracil on esophageal squamous cell carcinoma in vivo and in vitro.
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.
authors: The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China; School of Life Sciences, Zhengzhou University, Zhengzhou 450001, Henan, China.
authors: Yanting
authors: Y
authors: Zhang
authors: School of Life Sciences, Zhengzhou University, Zhengzhou 450001, Henan, China.
authors: Xiangzhan
authors: X
authors: Zhu
authors: School of Life Sciences, Zhengzhou University, Zhengzhou 450001, Henan, China.
authors: Tuanjie
authors: T
authors: Huang
authors: The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
authors: Lei
authors: L
authors: Chen
authors: School of Life Sciences, Zhengzhou University, Zhengzhou 450001, Henan, China.
authors: Yanxia
authors: Y
authors: Liu
authors: School of Life Sciences, Zhengzhou University, Zhengzhou 450001, Henan, China.
authors: Qinghua
authors: Q
authors: Li
authors: School of Life Sciences, Zhengzhou University, Zhengzhou 450001, Henan, China.
authors: Jishi
authors: J
authors: Song
authors: School of Life Sciences, Zhengzhou University, Zhengzhou 450001, Henan, China.
authors: Shanshan
authors: S
authors: Ma
authors: School of Life Sciences, Zhengzhou University, Zhengzhou 450001, Henan, China.
authors: Kun
authors: K
authors: Zhang
authors: The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. Electronic address: yangbo96@126.com.
authors: Bo
authors: B
authors: Yang
authors: The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China; School of Life Sciences, Zhengzhou University, Zhengzhou 450001, Henan, China. Electronic address: guanfangxia@126.com.
authors: Fangxia
authors: F
authors: Guan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004359:Drug Therapy, Combination; D004938:Esophageal Neoplasms / Q000188:drug therapy*; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy; D019207:beta Carotene / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D019207:beta Carotene; D005472:Fluorouracil
keywords: 5-Fluorouracil; Apoptosis; Esophageal cancer cells; Proliferation; β-Carotene