南方医科大学学报

南方医科大学学报 ›› 2022, Vol. 42 ›› Issue (4): 538-545.doi: 10.12122/j.issn.1673-4254.2022.04.09

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三七总皂苷联合环磷酰胺对荷肝癌H22细胞移植瘤小鼠的治疗作用

邹 琼，伍晓萍，王进吉，夏 谍，邓萌玥，丁俞珍，代玉玲，赵嵩月，陈 彤   

  1. 昆明医科大学药学院暨云南省天然药物药理重点实验室，云南 昆明 650500；云南省食品药品审核查验中心，云南 昆明 650228
  • 出版日期:2022-04-20 发布日期:2022-05-05

Therapeutic effect of Panax notoginseng saponins combined with cyclophosphamide in mice bearing hepatocellular carcinoma H22 cell xenograft

ZOU Qiong, WU Xiaoping, WANG Jinji, XIA Die, DENG Mengyue, DING Yuzhen, DAI Yuling, ZHAO Songyue, CHEN Tong   

  1. 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
  • Online:2022-04-20 Published:2022-05-05

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摘要： 目的 探究三七总皂苷（PNS）联合环磷酰胺（CTX）对肝癌H22荷瘤小鼠的治疗作用。方法 不同浓度的PNS体外干预肝癌H22细胞24~72 h后，CCK8比色法检测PNS对肝癌H22细胞增殖的影响；Annexin V/PI双荧光染色法检测PNS对肝癌H22细胞凋亡的影响；体内构建肝癌H22荷瘤小鼠模型，随机分为模型组、CTX组（25 mg/kg）、PNS低剂量组（120 mg/kg）、PNS中剂量组（240 mg/kg）、PNS 高剂量组（480 mg/kg）及 PNS 低剂量+CTX 组（120 mg/kg+25 mg/kg）、PNS 中剂量+CTX 组（240 mg/kg+25 mg/kg）、PNS高剂量+CTX组（480 mg/kg+25 mg/kg），连续给药10 d后处死小鼠，取材，检测PNS及PNS联合CTX对肝癌H22荷瘤小鼠单核-巨噬细胞的吞噬能力、脾淋巴细胞增殖能力、肿瘤坏死因子（TNF-α）、白介素-2（IL-2）的水平、血清溶血素抗体水平、血液指标、抑瘤率和生存期的影响。结果 PNS对肝癌 H22细胞的增殖抑制呈浓度依赖性，能显著促进肝癌H22细胞的凋亡（P<0.01）。体内单用PNS及PNS联合CTX能增强单核-巨噬细胞的吞噬、刺激脾淋巴细胞的增殖、促进TNF-α、IL-2释放、促进血清溶血素抗体的生成，增加外周血中白细胞、红细胞、淋巴细胞的数量，PNS高剂量+CTX组的抑瘤率高达83.28%（P<0.01）、生命延长率达131.25%（P<0.05）。结论 PNS及PNS与CTX联用可提高机体的免疫力和抑瘤率，延长肝癌H22荷瘤小鼠的生存期。

关键词: 三七总皂苷；肝癌；H22；免疫力；抑瘤率；生存期

Abstract: Objective To investigate the therapeutic effects of total saponins from Panax notognseng (PNS) combined with cyclophosphamide (CTX) in mice bearing hepatocellular carcinoma H22 cell xenograft. Methods We examined the effects of treatment with different concentrations of PNS on H22 cell proliferation for 24 to 72 h in vitro using CCK8 colorimetric assay. Annexin V/PI double fluorescence staining was used to detect the effect of PNS on apoptosis of H22 cells. Mouse models bearing H22 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-α), 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 H22 cells (P<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-α 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% (P<0.01) and a life prolonging rate of 131.25% in the mouse models (P<0.05). Conclusion PNS alone or in combination with CTX can improve the immunity and tumor inhibition rate and prolong the survival time of H22 tumor-bearing mice.

Key words: Panax notoginseng total saponins; liver cancer; H22 cells; immunity; anti-tumor rate; survival time