Antitumor immunostimulatory activity of polysaccharides from Salvia chinensis Benth
Antitumor immunostimulatory activity of polysaccharides from Salvia chinensis Benth
复制标题
丹参多糖的抗肿瘤免疫刺激活性。
DOI：
10.1016/j.jep.2015.03.065
复制
发表时间：
2015-06-20
影响因子：
5.4
通讯作者：
Xiang, Meixian
中科院分区：
文献类型：
--
作者：
Shu, Guangwen;Zhao, Wenhao;Xiang, Meixian
民族药理学相关性：鼠尾草（Salvia chinensis Benth（S.中药当归是治疗肝细胞癌（HCC）的传统中药。这种植物中含有丰富的多糖。然而，它仍然知之甚少，如果多糖从S。结论：PSSC具有抗肝癌活性。材料与方法：采用荷H22腹水型肝癌小鼠模型，观察PSSC的体内抗肝癌活性。通过测定一系列生理指标来评价对宿主动物的毒理作用。免疫细胞亚群通过磁激活细胞分选系统纯化并通过流式细胞术分析。逆转录实时荧光定量PCR和免疫印迹法检测PSSC对不同免疫细胞亚群细胞信号转导的影响。结果：PSSC在体内可抑制H22细胞的增殖，对荷瘤小鼠无明显毒性作用。PSSC减轻了肿瘤移植诱导的CD 4 + T细胞凋亡和血清细胞因子谱的失调，从而提高了自然杀伤细胞和CD 8 + T细胞的细胞毒活性。PSSC降低血清前列腺素E2（PGE 2）水平。注射外源性PGE_2可完全阻断PSSC的抗肿瘤免疫刺激活性。环磷酸腺苷（cAMP）是PGE 2的第二信使。在CD 4 + T细胞中，PSSC显著降低细胞内CAMP。这一事件升高了JAK 3的蛋白水平，增强了STAT 5磷酸化和STAT 5依赖的抗凋亡基因表达。环氧合酶-2是介导前列腺素E2生物合成的关键酶。PSSC抑制肿瘤相关巨噬细胞中环氧合酶-2的转录和翻译。结论：PSSC对移植性H22肝癌细胞具有抗肿瘤免疫刺激活性。抑制肿瘤移植诱导的PGE 2产生与PSSC的抗肿瘤免疫刺激活性有关。这些工作为传统的S。结论：PSSC具有抗肝癌的作用，支持PSSC作为肝癌临床治疗的辅助药物。(C)2015爱思唯尔爱尔兰有限公司版权所有。
Ethnopharmacological relevance: Salvia chinensis Benth (S. chinensis) is a traditional herb applied in the treatment of hepatocellular carcinoma (HCC). Polysaccharides abundantly exist in this plant. However, it remains poorly understood if polysaccharides from S. chinensis (PSSC) contribute to its anti-HCC activity. Materials and methods: The in vivo anti-HCC activity of PSSC was evaluated in Kunming mice bearing H22 ascitic hepatoma cells. An array of physiological indexes was measured to evaluate toxicological effects on host animals. Subgroups of immune cells were purified by a magnetic-activated cell sorting system and analyzed by flow cytometry. Reverse transcription real-time PCR and immunoblotting were recruited to determine the effects of PSSC on the cellular signaling of different subgroup of immune cells. Results: PSSC suppressed in vivo proliferation of H22 cells with undetectable toxic effects on tumor-bearing mice. PSSC alleviated tumor transplantation-induced CD4+ T cell apoptosis and dysregulation of serum cytokine profiles, which elevated cytotoxic activities of natural killer and CD8+ T cells. PSSC reduced serum levels of prostaglandin E2 (PGE2). Injection of exogenous PGE2 completely abrogated the antitumor immunostimulatory activity of PSSC. Cyclic adenosine monophosphate (cAMP) is the second messager of PGE2. In CD4+ T cells, PSSC substantially declined intracellular CAMP. This event elevated protein levels of JAK3, enhancing STAT5 phosphorylation and STAT5-depedent expression of antiapoptotic genes. Cyclooxygenase-2 is the key enzyme mediating biosynthesis of PGE2. PSSC suppressed the transcription and translation of cyclooxygenase-2 in tumor associated macrophages. Conclusion: Our data clearly showed antitumor immunostimulatory activity of PSSC against transplanted H22 HCC cells. Suppressing tumor transplantation-induced PGE2 production was implicated in the antitumor immunostimulatoly activity of PSSC. These works provides novel insights into the traditional application of S. chinensis against HCC and supported considering PSSC as an adjuvant reagent in clinical HCC treatment. (C) 2015 Elsevier Ireland Ltd. All rights reserved.