灵芝孢子油及灵芝提取物孢子油对乳腺癌血管生成调节因子的作用

张京 牛苗苗 杨丽 范莉莎 吴莉 战军*  张宏权

doi:10.3969/j.issn.0529-1356.2014.04.015

解剖学报 ›› 2014, Vol. 45 ›› Issue (4) : 525-530. DOI: 10.3969/j.issn.0529-1356.2014.04.015

肿瘤生物学

灵芝孢子油及灵芝提取物孢子油对乳腺癌血管生成调节因子的作用

张京¹ 牛苗苗¹ 杨丽¹ 范莉莎² 吴莉² 战军^1* 张宏权¹

作者信息 +

Effects of ganoderma lucidum spore oil and ganoderma lucidum extraction spore oil on angiogenesis regulatory factors

ZHANG Jing¹ NIU Miao-miao¹YANG Li¹ FAN Li-sha^２ WU Li^２ ZHAN Jun ^1* ZHANG Hong-quan¹

Author information +

文章历史 +

摘要

目的探讨灵芝孢子油及灵芝提取物孢子油对人源高恶性乳腺癌血管生成调节因子的作用。方法〖HTSS〗不同剂量的灵芝孢子油、灵芝提取物孢子油分别刺激体外培养的人源高恶性乳腺癌细胞系MDA-MB-231细胞及MDA-MB-231细胞制作的荷廇小鼠，Western blotting检测表皮生长因子受体（EGFR）的蛋白表达变化，Real-time PCR检测肿瘤血管生成相关因子EGFR、血管内皮生长因子（VEGF）、基质金属蛋白酶（MMPs）、血小板反应素-1（TSP-1）、血小板衍生因子（PDGF）、成纤维细胞生长因子（FGF）转录水平的基因表达变化。结果灵芝孢子油、灵芝提取物孢子油均可在体内和体外抑制人源高恶性乳腺癌细胞MDA-MB-231的EGFR蛋白表达，且有剂量依赖性；均可在体内和体外抑制VEGF RNA表达，增强血管生成抑制因子TSP-1 RNA表达；灵芝提取物孢子油比灵芝孢子油的作用更为显著。结论灵芝孢子油、灵芝提取物孢子油均有抑制肿瘤血管生成因子表达和促进血管生成抑制因子表达的作用, 其中灵芝提取物孢子油比灵芝孢子油的作用更为显著。

Abstract

Objective To study the role of ganoderma lucidum spore oil and ganoderma lucidum extraction spore oil in neovascularization of human high malignant breast cancer. Methods Human high malignant breast cancer cell MDA-MB-231 and tumor-bearing nude mice established with MDA-MB-231 were treated with different doses of ganoderma lucidum spore oil and ganoderma lucidum extraction spore oil. Epidermal growth factor receptor(EGFR) expression level was examined by Western blotting and the RNA expression levels of neovascularization related molecules such as EGFR, vascular endothelial growth factor(VEGF), metalloproteinases(MMPs), thrombospondin(TSP-1), platelet derived growth factor(PDGF), fibroblast growth factor(FGF) were detected by Real-time PCR. Results Both ganoderma lucidum spore oil and ganoderma lucidum extraction spore oil inhibited the expression of EGFR in vitroand in vivoin a dose-dependent way. Both compounds induced down-regulation of VEGF and up-regulation of TSP-1 at RNA level. The effect of Ganoderma lucidum extraction spore oil was more significant than that of ganoderma lucidum spore oil. Conclusion Both ganoderma lucidum spore oil and ganoderma lucidum extraction spore oil inhibite the expression of neovascularization related molecules and increase the expression of molecules inhibiting neovascularization, whereas the effect of ganoderma lucidum extraction spore oil is more obvious.

导出引用

张京牛苗苗杨丽范莉莎吴莉战军* 张宏权. 灵芝孢子油及灵芝提取物孢子油对乳腺癌血管生成调节因子的作用[J]. 解剖学报. 2014, 45(4): 525-530 https://doi.org/10.3969/j.issn.0529-1356.2014.04.015

ZHANG Jing NIU Miao-miao YANG Li FAN Li-sha WU Li ZHAN Jun* ZHANG Hong-quan. Effects of ganoderma lucidum spore oil and ganoderma lucidum extraction spore oil on angiogenesis regulatory factors[J]. Acta Anatomica Sinica. 2014, 45(4): 525-530 https://doi.org/10.3969/j.issn.0529-1356.2014.04.015

参考文献

［1］Wang Z, Wang N, Han S, et al. Dietary compound isoliquiritigenin inhibits breast cancer neoangiogenesis via VEGF/VEGF-2 signaling pathway［J］. PLos One, 2013,8(7):e68566.
［2］Wang B, Zhou KQ, Fan QSh, et al. Determination of triterpenoids and fatty acid in grass-cultivated ganoderma lucidum spores oil extracted by supercritical CO2［J］. Food & Machinery, 2006,22(1):74-75. (in Chinese)
王彬，周科勤，范青生，等.超临界CO2萃取菌草灵芝孢子油中三萜类物质和脂肪酸的测定［J］.食品与机械，2006,22（1）：74-75.
［3］Hu Sh, Yi YJ, Xiong XY, et al. Progress in research on ganoderma lucidum spore oil［J］. Journal of Anhui Agricultural Sciences, 2010,38(17):9214-9215. (in Chinese)
胡瞬，易有金，熊兴耀，等.灵芝孢子油的研究进展［J］。安徽农业科学，2010,38（17）：9214-9215.
［4］Patel S, Goyal A. Recent developments in mushrooms as anti-cancer therapeutics: a review［J］. 3 Biotech, 2012,2(1):1-15.
［5］Deepalakshmi K, Mirunalini S. Modulatory effect of Ganoderma lucidum on expression of xenobiotic enzymes, oxidant-antioxidant and hormonal status in 7,12-dimethylbenz(a)anthracene-induced mammary carcinoma in rats［J］. Pharmacogn Mag, 2013, 9(34): 167-175.
［6］Lu YZ, Wu XX, Chen S, et al. Effectiveness of Ganoderma lucidum preparation in treating simian acquired immune deficiency syndrome［C］. Zhongguo Yi Xue Ke Xue Yuan Xue Bao, 2011, 33(3):318-324.
［7］Zhou ZY, Tang YP, Xiang J, et al. Neuroprotective effects of water-soluble Ganoderma lucidum polysaccharides on cerebral ischemic injury in rats［J］. J Ethnopharmacol, 2010,131(1):154-164.
［8］Tan W, Lu J, Huang M, et al. Anti-cancer natural products isolated from chinese medicinal herbs［J］. Chin Med, 2011,6(1):27-42.
［9］Grothey A, Galanis E. Targeting angiogenesis: progress with anti-VEGF treatment with large molecules［J］. Nat Rev Clin Oncol, 2009,6(9):507-518.
［10］Scott A, Mellor H. VEGF receptor trafficking in angiogenesis［J］. Biochem Soc Trans, 2009,37(6):1184-1188.
［11］Gast RE, Knig S, Rose K, et al. Binding of ATP to vascular endothelial growth factor isoform VEGF-A165 is essential for inducing proliferation of human umbilical vein endothelial cells ［J］. BMC Biochem, 2011,12(1):28.
［12］Wen MJ, Qi YH, Bing GY. Effect of antisense VEGF₁₆₅ cDNA transfection on the growth of human neuroblastoma SH-SY5Y cellin vitro and in nude mice ［J］. Acta Anatomic Sinica, 2006, 37(1): 69-73. (in Chinese)
温铭杰，祁雅慧，邴国英. 反义VEGF₁₆₅ 基因转染对人神经母细胞瘤生物学行为的影响［J］. 解剖学报，2006,37（1）：69-73.
［13］Deryugina EI, Quigley JP, Pleiotropic roles of matrix metalloproteinases in tumor angiogenesis: contrasting, overlapping and compensatory functions ［J］. Biochim Biophys Acta, 2010,1803(1):103-120.
［14］Ratushny V, Astsaturov I, Burtness BA, et al. Targeting EGFR resistance networks in head and neck cancer ［J］. Cell Signal, 2009,21(8):1255-1268.

基金

国家自然科学基金资助项目Kindlin-1和Kindlin-2调控肺癌细胞可塑性的分子机制及其作为肺癌分化和预后标志物的研究;教育部博士点基金;国家自然科学基金资助项目；重编程产生Claudin-low/三阴乳腺癌干细胞：乳腺癌可塑性的分子机制及转化医学意义;北京市与中央在京高校共建项目;北京大学中央高校基本科研业务费资助