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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3.	劉金連, 王海芳, 馬淑惠, 等.羥基紅花黃色素A通過抑制動脈內皮細胞中TNFR1/NF-κB信號通路而發揮抗炎作用.細胞與分子免疫學雜志, 2015, 31:945-948.
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13.	銀瑞, 董新偉, 王錚.血管抑素基因治療Lewis肺癌移植瘤小鼠的療效研究.中華試驗外科雜志.2014, 31:768-2769.
14.	王更記, 楊文鋒, 付政, 等.非小細胞肺癌18F-FLT PET/CT顯像與腫瘤微血管密度的相關性.中華核醫學與分子影像雜志, 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.	尹華偉.紅花黃色素對肝癌H22荷瘤小鼠的抑瘤作用.中國現代醫生, 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.	顧汝軍, 王嶺, 姚青, 等.環磷酰胺抗血管生成化療抑制鼠S180皮下肉瘤血管形成的作用.第四軍醫大學學報, 2008, 29:74-76.
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1. Bhat TA, Singh RP. Tumor angiogenesis——a potential target in cancer chemoprevention. Food Chem Toxicol, 2008, 46:1334-1345.
2. 張前, 牛欣, 閆妍, 等.羥基紅花黃色素A抑制新生血管形成的機制研究.北京中醫藥大學學報, 2004, 27:25-29.
3. 劉金連, 王海芳, 馬淑惠, 等.羥基紅花黃色素A通過抑制動脈內皮細胞中TNFR1/NF-κB信號通路而發揮抗炎作用.細胞與分子免疫學雜志, 2015, 31:945-948.
4. 奚勝艷, 張前, 劉朝陽.羥基紅花黃色素A對裸鼠人胃腺癌BGC-823移植瘤抑制作用的研究.北京中醫藥大學學報, 2009, 32:331-335.
5. 謝軍平, 高亭, 李環羽, 等.羥基紅花黃色素A對小鼠Lewis肺癌移植瘤的抑制作用及VEGF的表達的影響.廣東醫學, 2014, 35:36-38.
6. 明平坡, 戈偉, 介芳芳, 等.恩度聯合放療對Lewis肺癌小鼠MVD及αvβ3 mRNA表達的影響.實用腫瘤學雜志, 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. 詹啟敏.分子腫瘤學.北京:人民衛生出版社, 2005, 215.
12. 高亭, 謝軍平, 段鳳英.抑制血管生成在肺癌治療中的研究進展.廣東醫學, 2012, 33:2353-2355.
13. 銀瑞, 董新偉, 王錚.血管抑素基因治療Lewis肺癌移植瘤小鼠的療效研究.中華試驗外科雜志.2014, 31:768-2769.
14. 王更記, 楊文鋒, 付政, 等.非小細胞肺癌18F-FLT PET/CT顯像與腫瘤微血管密度的相關性.中華核醫學與分子影像雜志, 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. 尹華偉.紅花黃色素對肝癌H22荷瘤小鼠的抑瘤作用.中國現代醫生, 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. 顧汝軍, 王嶺, 姚青, 等.環磷酰胺抗血管生成化療抑制鼠S180皮下肉瘤血管形成的作用.第四軍醫大學學報, 2008, 29:74-76.
20. 張前, 牛欣, 閆妍, 等.羥基紅花黃色素對體外培養人臍靜脈內皮細胞增殖的抑制作用.中國醫藥學報, 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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