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皂苷联合环磷酰胺对人肝癌H细胞异种移植瘤小鼠的治疗作用

[Therapeutic effect of saponins combined with cyclophosphamide in mice bearing hepatocellular carcinoma H cell xenograft].

作者信息

Zou Q, Wu X, Wang J, Xia D, Deng M, Ding Y, Dai Y, Zhao S, Chen T

机构信息

School of Pharmaceutical Science and Yunnan Provincial Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China.

Yunnan Food and Drug Inspection Center, Kunming 650228, China.

出版信息

Nan Fang Yi Ke Da Xue Xue Bao. 2022 Apr 20;42(4):538-545. doi: 10.12122/j.issn.1673-4254.2022.04.09.

Abstract

OBJECTIVE

To investigate the therapeutic effects of total saponins from (PNS) combined with cyclophosphamide (CTX) in mice bearing hepatocellular carcinoma H cell xenograft.

METHODS

We examined the effects of treatment with different concentrations of PNS on H cell proliferation for 24 to 72 h using CCK8 colorimetric assay. Annexin V/PI double fluorescence staining was used to detect the effect of PNS on apoptosis of H cells. Mouse models bearing H cell xenograft were established and treated with CTX (25 mg/kg), PNS (120, 240 or 480 mg/kg), alone or in combinations. After treatments for consecutive 10 days, the mice were euthanized for examinations of carbon clearance ability of the monocytes and macrophages, splenic lymphocyte proliferation, tumor necrosis factor (TNF-), interleukin-2 (IL-2), serum hemolysin antibody level, blood indicators, and the tumor inhibition rate.

RESULTS

Treatment with PNS concentration-dependently inhibited the proliferation and significantly promoted apoptosis of cultured H cells ( < 0.01). In the tumor-bearing mouse models, PNS alone and its combination with CTX both resulted in obvious enhancement of phagocytosis of the monocyte-macrophages, stimulated the proliferation of splenic lymphocytes, promoted the release of TNF- and IL-2 and the production of serum hemolysin antibody, and increased the number of white blood cells, red blood cells and lymphocytes in the peripheral blood. Treatment with 480 mg/kg PNS combined with CTX resulted in a tumor inhibition rate of 83.28% ( < 0.01) and a life prolonging rate of 131.25% in the mouse models ( < 0.05).

CONCLUSION

PNS alone or in combination with CTX can improve the immunity and tumor inhibition rate and prolong the survival time of H tumor-bearing mice.

摘要

目的

探讨三七总皂苷(PNS)联合环磷酰胺(CTX)对人肝癌H细胞裸鼠移植瘤的治疗作用。

方法

采用CCK8比色法检测不同浓度PNS作用24至72小时对H细胞增殖的影响。用Annexin V/PI双荧光染色法检测PNS对H细胞凋亡的影响。建立人肝癌H细胞裸鼠移植瘤模型,分别给予CTX(25 mg/kg)、PNS(120、240或480 mg/kg)单药或联合用药治疗。连续给药10天后,处死小鼠,检测单核细胞和巨噬细胞的碳廓清能力、脾淋巴细胞增殖能力、肿瘤坏死因子(TNF-)、白细胞介素-2(IL-2)、血清溶血素抗体水平、血液指标及肿瘤抑制率。

结果

PNS作用呈浓度依赖性抑制培养的H细胞增殖,并显著促进其凋亡(P<0.01)。在荷瘤小鼠模型中,PNS单药及其与CTX联合用药均能明显增强单核巨噬细胞的吞噬功能,刺激脾淋巴细胞增殖,促进TNF-和IL-2释放及血清溶血素抗体产生,增加外周血白细胞、红细胞及淋巴细胞数量。480 mg/kg PNS与CTX联合用药组小鼠模型的肿瘤抑制率为83.28%(P<0.01),生命延长率为131.25%(P<0.05)。

结论

PNS单药或联合CTX均可提高H荷瘤小鼠的免疫力和肿瘤抑制率,延长其生存时间。

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