Active hexose correlated compound potentiates the antitumor effects of low-dose 5-fluorouracil through modulation of immune function in hepatoma 22 tumor-bearing mice.
Active hexose correlated compound potentiates the antitumor effects of low-dose 5-fluorouracil through modulation of immune function in hepatoma 22 tumor-bearing mice.
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DOI：
10.4162/nrp.2015.9.2.129
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发表时间：
2015-04
影响因子：
2.4
通讯作者：
Liao L
中科院分区：
文献类型：
--
作者：
Cao Z;Chen X;Lan L;Zhang Z;Du J;Liao L
多种免疫调节剂可提高小剂量化疗药物的疗效。活性己糖相关化合物(AHCC)是一种蘑菇菌丝体提取物，已被证明是一种强大的免疫调节剂。小剂量5-氟尿嘧啶(5-FU)能否通过调节宿主免疫来增强小剂量5-FU的抗肿瘤作用尚不清楚。分别用PBS、5-FU(10 mg·kg-1·d-1，i.p)或AHCC(360 mg·kg-1·d-1，i.g)联合5-FU治疗H22荷瘤小鼠5d，用流式细胞仪检测外周血中CD3+、CD4+、CD8+和NK细胞的表达。生化方法测定ALT、AST、BUN、Cr水平。用放射免疫试剂盒检测血清中IL-2和肿瘤坏死因子α的表达，用原位末端标记法检测肿瘤细胞的凋亡。免疫组织化学染色检测Bax、Bcl2、TS蛋白表达，RT-PCR法检测基因表达水平。耗食量和体重测定结果表明，AHCC无明显毒性。AHCC可逆转5-FU所致的肝损伤和骨髓抑制(P<；0.05)。与5-FU组相比，AHCC+5-FU组小鼠的胸腺指数、外周血中CD3+、CD4+和NK细胞的百分比(P<；0.01)和CD4+/CD8+的比率(P<；0.01)均显著升高。放射免疫分析显示，与赋形剂组和5-FU组相比，联合用药组小鼠血清IL-2和肿瘤坏死因子α水平最高。更重要的是，与5-FU组相比，AHCC与5-FU联合应用可产生更强的抗肿瘤作用(P<；0.05)，并引起肿瘤组织中更严重的细胞凋亡(P<；0.05)。此外，AHCC联合5-FU进一步上调了Bcl2相关X蛋白(Bax)的表达(P<0.01)，而下调了B细胞淋巴瘤2(Bcl2)的表达(P<0.01)。这些结果支持了AHCC可能对接受化疗的癌症患者有益的说法。
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. 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. 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). These results support the claim that AHCC might be beneficial for cancer patients receiving chemotherapy.