Antitumor effect of Xiaojin Capsules on xenotransplanted tumor in zebrafish

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Aβ 25-35 NG108-15. 17. D. 2014 37 6 1029-1033. 13. 18. APP J. 2014 45 19 2757-2761. 14. SAMP8 253-258. D. 2013. 15. J. 2007 27 6 1112-1115.. 2012 21 6 670-674. 16. 21. SAMP8 /. 2012 27 3 289-291. 2009.. 2009 21 2 19. β 20. β J. 2011 17 3 32-33. SAMP10. 2004 21 3 51-57. 1 2 3 2 3 2 3 3 1. 430070 2. 430052 3. 310000 michigan cancer foundation-7 MCF-7 26. 47 88. 24 264. 72 μg /ml MCF-7 31. 66% 54. 35% 53. 77% P < 0. 01 264. 72 μg /ml 21. 74% 28. 92% P < 0. 01 MCF-7 R285. 5 doi 10. 3969 /j. issn. 1001-1528. 2016. 09. 005 A 1001-1528 2016 09-1902-05 Antitumor effect of Xiaojin Capsules on xenotransplanted tumor in zebrafish HUANG Zhi-jun 1 2 LAN Xiao-hong 3 ZHAO Gang 2 XU Yi-qiao 3 WU Mu-qin 2 ZHANG Yong 3 LI Chun-qi 3 1. School of Chemistry Chemical Engineering and Life Sciences Wuhan University of Technology Wuhan 430070 China 2. Jianmin Pharmaceutical Groups Co. Ltd. Wuhan 430052 China 3. Hangzhou Hunter Biotechnology Co. Ltd. Hangzhou 310000 China ABSTRACT AIM To investigate the antitumor effect of Xiaojin Capsules Moschus Momordicae Semen Aconiti kusnezoffii Radix cocta etc. in zebrafish models. METHODS The models for xenotransplanted tumor were established by zebrafish yolk sac xenotransplanted with fluorescent labeling human breast cancer cell line MCF-7. The zebrafish with xenotransplanted tumor was treated with Xiaojin Capsules by direct drug soaking for e- valuating their antitumor effect whose antiangiogenic activity was then observed by transgenic zebrafish. The in vivo 1902 2015-12-23 2014C03009 1972 Tel 027 84520229 E-mail 452354589@ qq. com

pro-apoptotic effect of this drug was evaluated based on image analysis after acridine orange staining. RESULTS The inhibition rates of Xiaojin Capsules with 26. 47 88. 24 and 264. 72 μg /ml on MCF-7 cell xenotransplanted tumor in zebrafish were 31. 66% 54. 35% and 53. 77% P < 0. 01 respectively. At the highest concentration 264. 72 mg /ml of Xiaojin Capsules the angiogenesis was markedly inhibited with the inhibition rate of 21. 74% P < 0. 01 and the cell apoptosis was significantly induced with the induction rate of 28. 92% P < 0. 01. CONCLUSION Xiaojin Capsules can induce the cell apoptosis and inhibit the growth of MCF-7 xenotransplanted tumor and angiogenesis which shows that this drug possesses potential antitumor effect. KEY WORDS Xiaojin Capsules zebrafish antiangiogenesis apoptosis induction antitumor Japan CP214 Ohaus Ameri- ca NIS-Elements D 3. 10 10 1. 3 AB Fli-1 28 1 1 L 200 mg 480 ~ 510 μs /cm ph 6. 9 ~ 7. 2 53. 7 ~ 71. 6 mg /L Ca- CO 3 SYXK 2012-0171 AAALAC 001458 2 2. 1 MCF-7 CM-Dil MCF-7 2-3 AB 4-5 MCF-7 6-8 35 24 h michigan cancer foundation- 7 MCF-7 3 26. 47 88. 24 264. 72 μg /ml 1 26. 47 88. 24 264. 72 μg /ml 1. 1 30 150217 Z10970132 25316-40-9 Sigma 1001523964 35 48 h 1 ng 20120202 10 Aldrich 494-38-2 1. 2 SZX7 Olympus FI MCF-7 Japan AZ100 Nikon Japan IM-300 Narishige FI MCF-7 5 = 1 - FI 100% 1903

2. 2 1 MCF-7 Fli-1 Tab. 1 Inhibition ratios of Xiaojin Capsules on MCF-7 xenotransplanted tumor 26. 47 88. 24 264. 72 μg /ml 258. 23 μg /ml 30 28 24 h 10 88. 24 547 087 ± 52 273 ** 54. 35 ** 264. 72 554 062 ± 44 050 ** 53. 77 ** S 10. 66% 264. 72 μg /ml = S -S 100% P < 0. 01 S 21. 74% 2. 3 AB 2 26. 47 2 88. 24 264. 72 μg /ml Tab. 2 Inhibition ratios of Xiaojin Capsules on angiogenesis n = 10 x ± 15 ng s 30 28 24 h 10 FS FS - FS = 100% FS 2. 4 x ± s Dunnett s t P < P < 0. 01 35. 45% 0. 05 26. 47 μg /ml 88. 24 μg /ml 3 3. 1 MCF-7-0. 26% 7. 76% 264. 72 μg /ml 1 ng MCF-7 P < 0. 01 30. 86% 28. 92% P < 0. 01 3 3 26. 47 88. 24 264. 72 μg /ml Tab. 3 Apoptosis-inducing rates of Xiaojin Capsules n = MCF-7 31. 66% 10 x ± s 54. 35% 53. 77% P < 0. 01 MCF-7 1 3. 2 258. 23 μg /ml P < 0. 01 23. 76% 26. 47 μg /ml 88. 24 μg /ml P > 0. 05 4 μg ml - 1 1 198 418 ± 87 704 1 ng / 828 624 ± 67 279 ** 30. 86 ** 26. 47 818 943 ± 65 819 ** 31. 66 ** μg ml - 1 / 5. 27 ± 0. 10 /% 10 4 /% 258. 23 4. 02 ± 0. 16 ** 23. 76 ** 26. 47 5. 24 ± 0. 25 0. 49 88. 24 4. 71 ± 0. 13 10. 66 264. 72 4. 12 ± 0. 16 ** 21. 74 ** 3. 3 P > 0. 05 /% μg ml - 1 10 5 1. 61 ± 0. 047 15 ng / 2. 18 ± 0. 048 ** 35. 45 ** 26. 47 1. 61 ± 0. 055-0. 26 88. 24 1. 74 ± 0. 059 7. 76 264. 72 2. 08 ± 0. 054 ** 28. 92 ** 0. 49% 1904

9 10-14 1. 2010 J. 2010. 3 2 Camus S Quevedo C Menéndez S et al. Identification of phosphorylase kinase as a novel therapeutic target through highthroughput screening for anti-angiogenesis compounds in ze- brafish J. Oncogene 2012 31 39 4333-4342. MCF-7 3 Tran T C Sneed B Haider J et al. Automated quantitative 4 Wang X Moon J Dodge M E et al. The development of high- zebrafish J ly potent inhibitors for porcupine 15 6 2700-2704. CD-31 16 and toxicity M Inc. 2011. J. Nat Rev Drug Discov 2005 4 1 35-44. 7402 cells J. Biochem Biophys Res Commun 2013. 1844-1846. 10. 38 2000 35 6 240. 11 8 17 1992 33 8 21-22. 12 J. 13 2000 16 6 30-31. 14 16 18-20 2005 19 6 501-502. 15 MMP-9 2007 15 5 326-328. MCF-7 J screening assay for antiangiogenic compounds using transgenic. Cancer Res 2007 67 23 11386-11392.. J Med Chem 2013 56 5 Rodrigues F S Yang X Nikaido M et al. A simple highly visual in vivo screen for anaplastic lymphoma kinase inhibitors J. ACS Chem Biol 2012 7 12 1968-1974. 6 Li C Q Luo L Q McGrath P. Methods for assessing drug safety. New Jersey John Wiley & Sons 7 Zon L I Peterson R T. In vivo drug discovery in the zebrafish 8 Hou Y Chu M Du F F et al. Recombinant disintegrin domain of ADAM15 inhibits the proliferation and migration of Bel- 640-645. 435 4 9. 2015 26 13.... 1990 10 6 343-344.. 86.... Ⅲ. 16 Agrawal S S Saraswati S Mathur R et al. Antitumor properties of Boswellic acid against Ehrlich ascites cells bearing mouse. Food Chem Toxicol 2011 49 9 1924-1934. 17 Inohara N Nunez G. Genes with homology to mammalian apoptosis regulators identified in zebrafish. Cell Death Differ 1905

2000 7 5 509. apoptosis in colon cancer cells and inhibits tumor growth in mu- 18. rine colorectal cancer xenografts. Cancer Lett 2009 279 201110442495 P. 1 93-100. 2013-06-26. 19 An M J Cheon J H Kim S W et al. Guggulsterone induces 20. GLC-82 D. 2012. 1 2 1 1 2 1 2 2 1 2* 1. 116622 2. 116622 E IgE LT EOS 40 mg /kg 10 mg /kg OVA 14 d 15 mg /kg 3 d 1 /d LT IgE ELISA BALF EOS LT IgE BALF EOS P < 0. 05 P < 0. 01 E R285. 5 doi 10. 3969 /j. issn. 1001-1528. 2016. 09. 006 A 1001-1528 2016 09-1906-04 Anti-type I allergy effect of quercetin on rats SHI Li-ying 1 2 DING Hui 1 LU Xuan 1 2 FENG Bao-min 1 2 WANG Yong-qi 2 YU Da-yong 1 2* 1. School of Life Sciences and Biotechnology Dalian University Dalian 116622 China 2. Institute of Materia Medica Dalian University Dalian 116622 China ABSTRACT AIM To investigate the effects of quercetin on the levels of IgE and leukotriene LT the number of eosinophils EOS and the area of inflammation in pulmonary tissue in IgE-induced type I allergy rats. METHODS The rats were randomly assigned to model montelukast high-dose 40 mg /kg and low-dose 10 mg /kg quercetin groups. Except for the control group untreated rats given with normal saline the rats in other groups were injected intraperitoneally with normal saline containing Al OH 3 and OVA and then administrated intravenously in tail vein with 15 mg /kg OVA 3 d once a day after 14 d for inducing typeⅠallergy. The LT and IgE levels in the serum of rats were assayed by ELISA the numbers of EOS in BALF and whole blood were counted by cell counting and the inflammation area in pulmonary tissue was evaluated by pathologic examination. RESULTS Compared with the model group the levels of IgE and LT in the serum the numbers of EOS in BALF and whole blood and the area of inflammation in pulmonary tissue were significantly reduced after being treated with high dose or low dose quercetin P < 0. 05 P < 0. 01. CONCLUSION Quercetin s inhibition of 2015-11-24 81073012 LJQ2013134 1975 E-mail shiliying99074@ 163. com * 1976 Tel 0411 87402107 E-mail yudayong @ dlu. edu. cn 1906