Effects of Hydroxysafflor Yellow A on Microvessel Density and mRNA Expression of Vascular Endothelial Growth Factor in Mice Transplanted Lewis Lung Cancer_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

 GaoTing ¹ , JiangYindi ² , LiuXiaowei ¹ , MaYujuan ¹ , HeXiaopeng ¹

1. Department of Respiratory Medicine, Xianyang Center Hospital, Xianyang, Shanxi, 712000, China;
2. ;

Corresponding author：

GaoTing, Email: gaoting828@126.com

Keywords：

Hydroxysafflor yellow A; Transplanted tumor of Lewis lung cancer; Microvessel density; Vascular endothelial growth factor

DOI：

10.7507/1671-6205.2016108

Video：

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Objective To observe the effects of hydroxysafflor yellow A (HSYA) on microvessel density (MVD) of mice transplanted Lewis lung cancer and mRNA expression of vascular endothelial growth factor (VEGF) so as to explore the tumor-inhibiting mechanism of HSYA. Methods Sixty tumor-bearing C57/BL mice were randomly divided into five groups, with 12 mice in each group, namely a control group, a cyclophosphamide (CTX) group (25mg/kg), a large dose HSYA group (112mg/L), a medium dose HSYA group (56mg/L), and a small dose HSYA group (28mg/L). These different drugs were administered by intraperitoneal injection. The mice were sacrificed 22 days after the treatment. Tumor tissues were sampled and examined by immunohistochemical method and quantitative real-time PCR to detect the expression of MVD and VEGF mRNA. Results The MVD of the medium and small dose HSYA groups and CTX group were 30.01±3.12, 22.56±2.11 and 16.21±2.40, respectively, which were significantly lower than 41.10±2.93 of the control group and 37.66±3.04 of the large dose HSYA group (χ²=2.82, P=0.010;χ²=3.16, P=0.007;χ²=4.58, P=0.000) and (χ²=1.98, χ²=0.038;χ²=2.45, P=0.016;χ²=3.82, P=0.001). The difference in VEGF amplified fluorescence expression threshold between the HSYA groups and the control group was not significant. However, after amplification, the expression of VEGF mRNA in the small dose HSYA group was only 0.43±0.16, which was obviously lower than 0.82±0.06 in the control group (F=0.77, P=0.038). Conclusion HSYA can significantly reduce MVD in mice transplanted Lewis lung cancer and down-regulate expression of VEGF mRNA to achieve tumor-inhibiting effect.

Citation： Gao Ting, Jiang Yindi, Liu Xiaowei, Ma Yujuan, He Xiaopeng. Effects of Hydroxysafflor Yellow A on Microvessel Density and mRNA Expression of Vascular Endothelial Growth Factor in Mice Transplanted Lewis Lung Cancer. Chinese Journal of Respiratory and Critical Care Medicine, 2016, 15(5): 461-464. doi: 10.7507/1671-6205.2016108 Copy

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14.	王更记, 杨文锋, 付政, 等.非小细胞肺癌18F-FLT PET/CT显像与肿瘤微血管密度的相关性.中华核医学与分子影像杂志, 2015, 35:1-4.
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17.	Chang JM, Hung LM, Chyan YJ, et al. Carthamus tinctorius enhances the antitumor activity of dendritic cell vaccines via polarization toward Th1 cytokines and increase of cytotoxic T lymphocytes. Evid Based Complement Alternat Med, 2011, 2011:2748-2758.
18.	He HB, Liu QJ, She MQ, et al. Cardioprotective effects of hydroxysafflor yellow A on diabetic cardiac insufficiency attributed to up-regulation of the expression of intracellular calcium handling proteins of sarcoplasmic reticulum in rats. Phytother Res, 2008, 22:1107-1114.
19.	顾汝军, 王岭, 姚青, 等.环磷酰胺抗血管生成化疗抑制鼠S180皮下肉瘤血管形成的作用.第四军医大学学报, 2008, 29:74-76.
20.	张前, 牛欣, 闫妍, 等.羟基红花黄色素对体外培养人脐静脉内皮细胞增殖的抑制作用.中国医药学报, 2004, 19:379-381.

1. Bhat TA, Singh RP. Tumor angiogenesis——a potential target in cancer chemoprevention. Food Chem Toxicol, 2008, 46:1334-1345.
2. 张前, 牛欣, 闫妍, 等.羟基红花黄色素A抑制新生血管形成的机制研究.北京中医药大学学报, 2004, 27:25-29.
3. 刘金连, 王海芳, 马淑惠, 等.羟基红花黄色素A通过抑制动脉内皮细胞中TNFR1/NF-κB信号通路而发挥抗炎作用.细胞与分子免疫学杂志, 2015, 31:945-948.
4. 奚胜艳, 张前, 刘朝阳.羟基红花黄色素A对裸鼠人胃腺癌BGC-823移植瘤抑制作用的研究.北京中医药大学学报, 2009, 32:331-335.
5. 谢军平, 高亭, 李环羽, 等.羟基红花黄色素A对小鼠Lewis肺癌移植瘤的抑制作用及VEGF的表达的影响.广东医学, 2014, 35:36-38.
6. 明平坡, 戈伟, 介芳芳, 等.恩度联合放疗对Lewis肺癌小鼠MVD及αvβ3 mRNA表达的影响.实用肿瘤学杂志, 2014, 28:1-6.
7. Brzozowa M, Michalski M, Harabin-Slowinska M, et al. The role of tumour microenvironment in gastric cancer angiogenesis. Prz Gastroenterol, 2014, 9:325-328.
8. Barzi A, Thara E. Angiogenesis in esophageal and gastric cancer:a paradigm shift in treatment. Expert Opin Biol Ther, 2014, 14:1319-1332.
9. David L, Mallet C, Keramidas M, et al. Bone morphogenetic protein-9 is a circulating vascular quiescence factor. Circ Res, 2008, 102:914-922.
10. Mulkeen AL, Silva T, Yoo PS, et al. Short interfering RNA-mediated gene silencing of vascular endothelial growth factor:effects on cellular proliferation in colon cancer cells. Arch Surg, 2006, 141:367-374.
11. 詹启敏.分子肿瘤学.北京:人民卫生出版社, 2005, 215.
12. 高亭, 谢军平, 段凤英.抑制血管生成在肺癌治疗中的研究进展.广东医学, 2012, 33:2353-2355.
13. 银瑞, 董新伟, 王铮.血管抑素基因治疗Lewis肺癌移植瘤小鼠的疗效研究.中华试验外科杂志.2014, 31:768-2769.
14. 王更记, 杨文锋, 付政, 等.非小细胞肺癌18F-FLT PET/CT显像与肿瘤微血管密度的相关性.中华核医学与分子影像杂志, 2015, 35:1-4.
15. Xi SY, Zhang Q, Liu CY, et al. Effects of hydroxy safflower yellow-A on tumor capillary angiogenesis in transplanted human gastric adenocarcinoma BGC-823 tumors in nude mice. J Tradit Chin Med, 2012, 32:243-248.
16. 尹华伟.红花黄色素对肝癌H22荷瘤小鼠的抑瘤作用.中国现代医生, 2012, 50:3-6.
17. Chang JM, Hung LM, Chyan YJ, et al. Carthamus tinctorius enhances the antitumor activity of dendritic cell vaccines via polarization toward Th1 cytokines and increase of cytotoxic T lymphocytes. Evid Based Complement Alternat Med, 2011, 2011:2748-2758.
18. He HB, Liu QJ, She MQ, et al. Cardioprotective effects of hydroxysafflor yellow A on diabetic cardiac insufficiency attributed to up-regulation of the expression of intracellular calcium handling proteins of sarcoplasmic reticulum in rats. Phytother Res, 2008, 22:1107-1114.
19. 顾汝军, 王岭, 姚青, 等.环磷酰胺抗血管生成化疗抑制鼠S180皮下肉瘤血管形成的作用.第四军医大学学报, 2008, 29:74-76.
20. 张前, 牛欣, 闫妍, 等.羟基红花黄色素对体外培养人脐静脉内皮细胞增殖的抑制作用.中国医药学报, 2004, 19:379-381.

Chinese Journal of Respiratory and Critical Care Medicine

Effects of Hydroxysafflor Yellow A on Microvessel Density and mRNA Expression of Vascular Endothelial Growth Factor in Mice Transplanted Lewis Lung Cancer

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