Active hexose correlated compound potentiates the antitumor effects of low-dose 5-fluorouracil through modulation of immune function in hepatoma 22 tumor-bearing mice.
- Author:
Zhiyun CAO
1
;
Xuzheng CHEN
;
Lan LAN
;
Zhideng ZHANG
;
Jian DU
;
Lianming LIAO
Author Information
- Publication Type:Original Article
- Keywords: Muschroom; 5-fluorouracil; toxicity; hepatocarcinoma; immune
- MeSH: Agaricales; Animals; Apoptosis; Body Weight; Carcinoma, Hepatocellular*; Diet; Drug Therapy; Flow Cytometry; Fluorouracil*; Humans; Immunologic Factors; In Situ Nick-End Labeling; Interleukin-2; Killer Cells, Natural; Liver; Lymphoma, B-Cell; Mice*; Radioimmunoassay; RNA, Messenger; Thymus Gland; Tumor Necrosis Factor-alpha
- From:Nutrition Research and Practice 2015;9(2):129-136
- CountryRepublic of Korea
- Language:English
- Abstract: BACKGROUND/OBJECTIVES: A variety of immunomodulators can improve the efficacy of low-dose chemotherapeutics. Active hexose correlated compound (AHCC), a mushroom mycelia extract, has been shown to be a strong immunomodulator. Whether AHCC could enhance the antitumor effect of low-dose 5-fluorouracil (5-FU) via regulation of host immunity is unknown. MATERIALS/METHODS: In the current study Hepatoma 22 (H22) tumor-bearing mice were treated with PBS, 5-FU (10 mg.kg-1.d-1, i.p), or AHCC (360 mg.kg-1.d-1, i.g) plus 5-FU, respectively, for 5 d. CD3+, CD4+, CD8+, and NK in peripheral blood were detected by flow cytometry. ALT, AST, BUN, and Cr levels were measured by biochemical assay. IL-2 and TNFalpha in serum were measured using the RIA kit and apoptosis of tumor was detected by TUNEL staining. Bax, Bcl-2, and TS protein levels were measured by immunohistochemical staining and mRNA level was evaluated by RT-PCR. RESULTS: Diet consumption and body weight showed that AHCC had no apparent toxicity. AHCC could reverse liver injury and myelosuppression induced by 5-FU (P < 0.05). Compared to mice treated with 5-FU, mice treated with AHCC plus 5-FU had higher thymus index, percentages of CD3+, CD4+, and NK cells (P < 0.01), and ratio of CD4+/CD8+ (P < 0.01) in peripheral blood. Radioimmunoassay showed that mice treated with AHCC plus 5-FU had the highest serum levels of IL-2 and TNFalpha compared with the vehicle group and 5-FU group. More importantly, the combination of AHCC and 5-FU produced a more potent antitumor effect (P < 0.05) and caused more severe apoptosis in tumor tissue (P < 0.05) compared with the 5-FU group. In addition, the combination of AHCC and 5-FU further up-regulated the expression of Bcl-2 associated X protein (Bax) (P < 0.01), while it down-regulated the expression of B cell lymphoma 2 (Bcl-2) (P < 0.01). CONCLUSIONS: These results support the claim that AHCC might be beneficial for cancer patients receiving chemotherapy.
