目的 研究裂果薯总皂苷(SSPHs)对H22荷瘤小鼠的抑瘤作用及其机制。方法 建立H22荷瘤小鼠模型,连续给药15 d后,剖取并测量瘤组织,计算抑瘤率、脏器指数。ELISA法检测小鼠血清中相关细胞因子含量,HE染色观察肿瘤病理学变化,免疫组化法检测肿瘤组织中CD4+T和CD8+T细胞的浸润情况。结果 SSPHs抑瘤率为61.70%。SSPHs明显提高荷瘤小鼠的胸腺指数以及血清中白细胞介素(IL)-2、肿瘤坏死因子(TNF)-α水平,降低IL-10水平,降低肝脏指数。HE染色结果显示,模型组坏死区域少,而实验组肿瘤细胞核固缩,有明显的坏死区域。免疫组化结果显示,实验组肿瘤组织中CD4+T和CD8+T细胞浸润明显。结论 SSPHs明显抑制H22荷瘤小鼠肿瘤的生长,其机制可能与其调节细胞因子,提高抗肿瘤免疫,增强机体免疫调节活性有关。
Abstract
OBJECTIVE To investigate the anti-tumor effect and related mechanism of total saponins of Schizocapsa plantaginea Hance(SSPHs) on H22-bearing mice. METHODS A H22 tumor-bearing mice model was established. After 15 d of continuous administration, the tumors, livers, spleens, and thymuses were dissected and measured to calculate tumor inhibition rate and organ indexes. ELISA assay was used to detect the levels of IL-2, IL-10, IL-12 and TNF-α in the serum of mice, HE staining was used to observe the tumor pathological alterations, and immunohistochemical assay was used to detect the infiltration of CD4+ T and CD8+ T cells in the tumor tissues. RESULTS The inhibition rate of SSPHs was 61.70%. SSPHs significantly increased the thymus index and decreased the liver index, additionally, it significantly increased the levels of IL-2 and TNF-α in the serum of mice, decreased the level of IL-10. The RESULTS of HE staining showed that fewer areas of necrosis in the model group, while tumor cells with nucleus contraction and obvious areas of necrosis in the SSPHs group. Immunohistochemical RESULTS showed that SSPHs significantly increased the infiltration of CD4+ T and CD8+ T cells in tumor tissues. CONCLUSION SSPHs significantly inhibits the growth of H22 tumors, and its mechanism may be associated with the abilities of regulating cytokines, improving anti-tumor immunity, and enhancing the immune regulatory activity.
关键词
裂果薯总皂苷 /
H22荷瘤小鼠 /
肿瘤免疫 /
免疫调节 /
细胞因子
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Key words
total saponins of Schizocapsa plantaginea Hance /
H22 tumor-bearing mice /
tumor immunity /
immunomodulation /
cytokines
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中图分类号：
R965
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参考文献
[1] TORRE L A, BRAY F, SIEGEL R L, et al. Global cancer statistics, 2012 [J]. CA Cancer J Clin, 2015, 65(2):87-108.
[2] El-SERAG H B, RUDOLPH K L. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis [J]. Gastroenterology, 2007, 132(7):2557-2576.
[3] FU Y, SILVERSTEIN S, MCCUTCHEON J N, et al. An endogenous DNA adduct as a prognostic biomarker for hepatocarcinogenesis and its prevention by theaphenon E in mice [J]. Hepatology, 2018, 67(1):159-170.
[4] ZHENG X, MA W, SUN R, et al. Butaselen prevents hepatocarcinogenesis and progression through inhibiting thioredoxin reductase activity [J]. Redox Biol, 2018, 14:237-249.
[5] EL-SERAG H B. Epidemiology of viral hepatitis and hepatocelluLar carcinoma [J]. Gastroenterology, 2012, 142(6):1264-1273.
[6] LIN S, HOFFMANN K, SCHEMMER P. Treatment of hepatocellular carcinoma: a systematic review [J]. Liver Cancer, 2012, 1(3-4):144-158.
[7] FITZMAURICE C, ALLEN C, BARBER R M, et al. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: a systematic analysis for the global burden of disease study [J]. JAMA Oncol, 2017, 3(4):524-548.
[8] QIU F L, ZHOU J, PU Q L. Two new steoidal saponins from Tacca plantaginea root [J]. Acta Bot Yunnan(云南植物研究), 1985, 7(2):225-231.
[9] LUO S R, QIU H C, LIANG G, et al. The characteristic spectra of saponins of Schizocapsa plantaginea hance and the antitumor activity of effective components in the total saponins [J]. Nat Prod Res Dev(天然产物研究与开发), 2018, 30(2):294-298.
[10] SUN Y W, QIU H C, OU M C, et al. Saponins isolated from Schizocapsa plantaginea inhibit human hepatocellular carcinoma cell growth in vivo and in vitro via mitogen-activated protein kinase signaling [J]. Chin J Nat Med(中国天然药物), 2018, 16(1):29-40.
[11] LIAO Z H, CHEN Y Y, HUANG X Y, et al. Effects of total saponins of Schizocapsa plantaginea Hance on hepatic fibrosis in rats and its mechanism[J]. Chin Pharmacol Bull (中国药理学通报), 2019, 35(5):624-629.
[12] HUANG X Y, LU G D, LIAO Z H, et al. Effects of Schizocapsa plantaginea saponins on autophagy of human liver cancer BEL-7402 cells[J]. J Chin Med Mater (中药材), 2019,42(1):178-183.
[13] DONG M X, MENG Z F, KUERBAN K, et al. Diosgenin promotes antitumor immunity and PD-1 antibody efficacy against melanoma by regulating intestinal microbiota [J]. Cell Death Dis, 2018, 9(10): 1039.
[14] WANG Y, LU B F, JIANG J T. The role of tumor infiltrating lymphocytes and their subgroups in tumor immunity[J]. Chin J Clin Lab Sci (临床检验杂志), 2018, 36(11):854-857.
[15] YAN L J, ZOU S J, GONG A F, et al. Inhibition of total flavonids from Cudrania tricuspidata Bun on Lewis lung cancer and the effect of its component compatibility on autophagy of LLC cells[J]. Chin Pharm J (中国药学杂志), 2019, 54(21):1773-1780.
[16] LIU Y, LU G S, WANG L, et al. Antitumor effect of alcohol extract of Pileostegia tomentella on H22 tumor-bearing mice[J]. Chin Pharm J(中国药学杂志),2016, 51(12):981-984.
[17] LIU L L, KANG Z L, ZHU Y K. Cytokines and tumor immunity[J]. Shanxi Med J(山西医药杂志), 2013, 42(11):1250-1252.
[18] SHAN B E. IL-12 family cytokines: hot molecules in tumor immunotherapy research[J]. Chin J Cancer Biother (中国肿瘤生物治疗杂志), 2011, 18(3):239-243.
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脚注
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基金
国家自然科学基金项目资助(81460620)
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