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维康福颗粒复方对荷瘤小鼠的抗肿瘤及免疫调节作用

Antitumor and immunomodulatory effects of weikangfu granule compound in tumor-bearing mice.

作者信息

Nie Xiaohua, Shi Baojun, Ding Yuting, Tao Wenyi

机构信息

College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou, People's Republic of China.

Guangdong VTR Bio-Tech Co., Ltd., Zhuhai, People's Republic of China.

出版信息

Curr Ther Res Clin Exp. 2006 Mar;67(2):138-50. doi: 10.1016/j.curtheres.2006.04.002.

Abstract

BACKGROUND

Weikangfu granule compound (WKC) is a drug preparation based on a clinical prescription drug, Weikangfu-tang, which has been found to have therapeutic effects on gastric cancer. WKC comprises 7 components, including polysaccharides, saponin, flavonoids, and essential oil.

OBJECTIVE

The purpose of this study was to assess the antitumor and immunomodulatory effects of WKC in a tumor-bearing rodent model.

METHODS

Male and female Kuming mice weighing ∼20 g were subcutaneously implanted with sarcoma 180 (S180) tumor cells and randomly assigned to 1 of 5 treatment groups: oral WKC 175, 350, or 525 mg/kg·d, isotonic saline (negative control), or intraperitoneal cyclophosphamide 25 mg/kg·d (positive control). All treatments were administered daily for 10 days. After euthanization on day 11, the mice, tumors, and spleens were weighed. Lymphocyte proliferation and cytotoxic T lymphocyte (CTL) activity were determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cellular viability assay method. Macrophage phagocytosis was identified using a yeast test.

RESULTS

Fifty mice were included in the study (10 mice were assigned to each group). The tumors of the mice administered WKC 175, 350, and 525 mg/kg·d were significantly regressed, as determined using MICs, compared with those in the negative-control group (P<0.05, P<0.01, and P<0.01, respectively), and the inhibitory rates were 30.43%, 46.72%, and 54.35%, respectively. Compared with those in the negative-control group, CTL activities and lymphocyte proliferations in the presence of concanavalin A were significantly greater in the WKC-treated groups at all doses (CTL activities: P<0.05, P<0.01, and P<0.01, respectively; lymphocyte proliferations: P<0.05, P<0.01, and P<0.01, respectively). In the groups receiving WKC 175, 350, and 525 mg/kg·d, the phagocytic rates were 1.5- to 2.0-fold those in the negative-control group (P<0.05, P<0.01, and P<0.01, respectively). In the groups receiving WKC 175, 350, and 525 mg/kg·d, the phagocytic indexes were 3.7- to 5.0-fold those in the negative-control group (all, P<0.01). In contrast, lymphocyte proliferation in the positive-control group was significantly less compared with that in the negative-control group (P<0.01), but no significant differences were found in CTL activities or macrophage phagocytosis between these 2 groups.

CONCLUSION

The results of this study in a rodent model suggest that WKC exhibited antitumor and immunomodulatory activities in S180-bearing mice, and that WKC improved nonspecific and specific immune functions in mice, such as lymphocyte proliferation, CTL activity, and macrophage phagocytosis.

摘要

背景

维康福复方颗粒(WKC)是一种基于临床处方药维康福汤研制的药物制剂,已发现其对胃癌具有治疗作用。WKC包含多糖、皂苷、黄酮类化合物和挥发油等7种成分。

目的

本研究旨在评估WKC在荷瘤啮齿动物模型中的抗肿瘤和免疫调节作用。

方法

将体重约20 g的雄性和雌性昆明小鼠皮下接种肉瘤180(S180)肿瘤细胞,并随机分为5个治疗组之一:口服WKC 175、350或525 mg/kg·d、等渗盐水(阴性对照)或腹腔注射环磷酰胺25 mg/kg·d(阳性对照)。所有治疗均每日给药,持续10天。在第11天安乐死后,称取小鼠、肿瘤和脾脏的重量。采用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐细胞活力测定法测定淋巴细胞增殖和细胞毒性T淋巴细胞(CTL)活性。采用酵母试验鉴定巨噬细胞吞噬作用。

结果

本研究共纳入50只小鼠(每组10只)。与阴性对照组相比,给予WKC 175、350和525 mg/kg·d的小鼠肿瘤明显消退(分别采用最小抑菌浓度法测定,P<0.05、P<0.01和P<0.01),抑制率分别为30.43%、46.72%和54.35%。与阴性对照组相比,所有剂量WKC治疗组在伴刀豆球蛋白A存在时的CTL活性和淋巴细胞增殖均显著增强(CTL活性:分别为P<0.05、P<0.01和P<0.01;淋巴细胞增殖:分别为P<0.05、P<0.01和P<0.01)。在接受WKC 175、350和525 mg/kg·d的组中,吞噬率是阴性对照组的1.5至2.0倍(分别为P<0.05、P<0.01和P<0.01)。在接受WKC 175、350和525 mg/kg·d的组中,吞噬指数是阴性对照组的3.7至5.0倍(均为P<0.01)。相比之下,阳性对照组的淋巴细胞增殖与阴性对照组相比显著降低(P<0.01),但两组之间的CTL活性或巨噬细胞吞噬作用无显著差异。

结论

本研究在啮齿动物模型中的结果表明,WKC在荷S180小鼠中表现出抗肿瘤和免疫调节活性,并且WKC改善了小鼠的非特异性和特异性免疫功能,如淋巴细胞增殖、CTL活性和巨噬细胞吞噬作用。

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