中国肿瘤生物治疗杂志2023，Vol.30Issue(11)：957-964,8.DOI:10.3872/j.issn.1007-385x.2023.11.004
基于"正虚伏毒"理论探讨金复康有效组分调控NK细胞功能抑制Lewis肺癌细胞的转移
Study on the effective components of Jinfukang in regulating the function of NK cells and inhibiting the metastasis of lung cancer Lewis cells based on"Deficiency of Vital Qi and Hidden Toxin"theory
摘要
Abstract
Objective:To explore the immunological mechanism of the effective components in Jinfukang,astragaloside Ⅳ and paris saponins Ⅶ,in inhibiting lung cancer Lewis cells metastasis based on the theory of"Deficiency of Vital Qi and Hidden Toxin".Methods:The animal model of lung cancer metastasis was established by injecting Lewis cells into the tail vein of C57BL/6J mice.The model mice were randomly divided into a treatment group and a control group according to the random table method,8 mice per group.The treatment group was intervened with Jinfukang effective components,astragaloside Ⅳ(25 mg/kg)and with paris saponins Ⅶ(2.5 mg/kg).Four weeks later,the lung and liver metastases were observed.The histopathological changes of lung and liver metastatic foci were observed by H-E staining.The proportions of NK cells in peripheral blood and spleen tissues were detected by flow cytometry.The levels of TNF-α and IFN-γ in serum were detected by ELISA.The protein expression of Ki-67 in the metastatic foci was detected by immunohistochemical method,and the infiltration of NK cells and the secretion of IFN-γ in the metastatic foci were detected by immunofluorescence.The NK cells in the spleen of healthy mice were separated by immunomagnetic beads and co-cultured with astragaloside Ⅳ(5 μmol/L),paris saponins Ⅶ(0.5 μmol/L),and Lewis cells that intervened by both drugs.The degranulation level of NK cells was detected by flow cytometry,and the killing activity of NK cells against Lewis cells was detected by LDH method.Results:Compared with the control group,the number and load of lung and liver metastases were significantly decreased(both P<0.05),The transfer load is also significantly reduced(both P<0.05),and the expression of Ki-67 protein in the metastatic foci was significantly reduced(P<0.05)in the mice treated with astragaloside Ⅳ and paris saponins Ⅶ;the infiltration level of NK cells in metastatic tumor tissue was significantly increased,and IFN-γ was released from intracellular to extracellular of NK cells.In addition,the proportion of NK cells in spleen decreased significantly(P<0.05),while the level of NK cells in peripheral blood increased significantly(P<0.05).The level of IFN-γ in serum of mice decreased significantly(P<0.05),while the level of TNF-α increased significantly(all P<0.05).In vitro study found that the degranulation level of NK cells increased significantly(P<0.05)after single or combined intervention of astragaloside Ⅳ and paris saponins Ⅶ,which,however,had no significant effect on the killing activity of NK cells against Lewis cells(P>0.05).Conclusion:The combined use of astragaloside Ⅳ and paris saponins Ⅶ,the effective components of Jinfukang,can promote the infiltration of NK cells into tumor tissues and increase the secretion of IFN-γ to inhibit the the lung and liver metastasis of Lewis cells,provides a convincing experimental case for the"Deficiency of Vital Qi and Hidden Toxin"theory.关键词
肺癌/Lewis细胞/金复康/正虚伏毒/转移/NK细胞/重楼皂苷Ⅶ/黄芪甲苷ⅣKey words
lung cancer/Lewis cell/Jinfukang/Deficiency of Vital Qi and Hidden Toxin/metastasis/NK cell/paris saponins Ⅶ/astragaloside Ⅳ分类
医药卫生引用本文复制引用
于盼,田建辉,陆鑫熠,罗斌,阙祖俊..基于"正虚伏毒"理论探讨金复康有效组分调控NK细胞功能抑制Lewis肺癌细胞的转移[J].中国肿瘤生物治疗杂志,2023,30(11):957-964,8.基金项目
国家自然科学基金项目(No.81973517,No.82174245,No.8214943,No.82174017) （No.81973517,No.82174245,No.8214943,No.82174017）
上海市卫生健康委领军人才基金(No.2022LJ014) （No.2022LJ014）
上海市中医医院未来计划科技发展基金项目(No.WL-HBRC-2021001K) （No.WL-HBRC-2021001K）
上海市进一步加快中医传承创新发展三年行动计划[No.ZY(2021-2023)-0211] （2021-2023）
