title: Active hexose correlated compound potentiates the antitumor effects of low-dose 5-fluorouracil through modulation of immune function in hepatoma 22 tumor-bearing mice.
abstract: OBJECTIVE
  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.
  
  
  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 TNFα 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 TNFα 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.
authors: Fujian Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Huatuo Road, No1, Fuzhou, 350108, China.
authors: Zhiyun
authors: Z
authors: Cao
authors: Fujian Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Huatuo Road, No1, Fuzhou, 350108, China.
authors: Xuzheng
authors: X
authors: Chen
authors: The Second People's Hospital of Fujian Province, China.
authors: Lan
authors: L
authors: Lan
authors: Inspection and Quarantine Technique Centre of Fujian Entry-exit Inspection and Quarantine Bureau, China.
authors: Zhideng
authors: Z
authors: Zhang
authors: The Second People's Hospital of Fujian Province, China.
authors: Jian
authors: J
authors: Du
authors: Fujian Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Huatuo Road, No1, Fuzhou, 350108, China.
authors: Lianming
authors: L
authors: Liao
keywords: 5-fluorouracil; Muschroom; hepatocarcinoma; immune; toxicity