117 1002-0217 2016 02-0117 - 05 5-1 2 1 2 1 2 1. 2. 241002 5- CT26 CT26 5-5- 5- R 285. 5 A DOI 10. 3969 / j. issn. 1002-0217. 2016. 02. 004 Antitumor activity of an exopolysaccharide from Trichoderma pseudokoningii complexes carrying 5-fluorouracil on CT26-tumor bearing mice ZHU Lei LU Jingbo CHEN Kaoshan Department of Pharmacy Wannan Medical College Wuhu 241002 China Abstract Objective To observe the antitumor effect of exopolysaccharide EPS from Trichoderma pseudokoningii containing 5-fluorouracil 5-FU in tumor bearing mice using in vivo technique. Methods CT26-tumor bearing mouse models were developed and the effects of EPS on inhibition of the tumor and physiological indexes were determined. Results Combined EPS with 5-FU significantly inhibited the CT26 tumor growth in a dose-dependent manner and the inhibition rate in CT26 tumor was higher using the complexes than simple 5-FU. Still the physiological index and the quality of life were improved in the tumor bearing mice after intervention with EPS plus 5-FU. Conclusion Combined EPS with 5-FU presents enhanced antitumor activity and EPS could attenuate toxicity effect induced by 5-FU. Key words Trichoderma pseudokoningii exopolysaccharide antitumor activity immunoregulation 1408085MH197 KJ2015A199 2012jc14 2015-10-20 1990-2013 13685532095 llz4925@ 163. com ksc313@ 126. com. 4. 9 LI X PABLA N WEI Q et al. PKC-delta promotes renal tubular -α -1β J. cell apoptosis associated with proteinuria J. J Am Soc Nephrol 2009 28 9 1114-1116. 5 NAVANEETHAN S D NIGWEKAR S U STRIPPOLI GF. Aldosterone antagonists for preventing the progression of chronic kidney disease J. Cochrane Database of Systematic Reviews 2014 4 4 297-301. 6 QIU W ZHOU J ZHU G et al. Sublytic C5b-9 triggers glomerular mesangial cell apoptosis via XAF1 gene activation mediated by p300-dependent IRF-1 acetylation J. Cell Death Dis 2014 5 4 e1176. 7 CHEN KC PENG CC HSIEH CL et al. Exercise ameliorates renal cell apoptosis in chronic kidney disease by intervening in the intrinsic and the extrinsic apoptotic pathways in a rat model J. Evid Based Complement Alternat Med 2013 2013 6 368450. 8. directly to Atg8 / LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy J. J Biol Chem 2007 282 33 J. 2013 26 11 1129-1133. 2010 21 7 1115-1124. 10. J. 2012 13 9 836-838. 11 DONG Z. Introduction autophagy in kidneys J. Semin Nephrol 2014 34 1 1. 12 RUBINSTEIN AD KIMCHI A. Life in balance-a mechanistic view of the crosstalk between autophagy and apoptosis J. J Cell Sci 2012 125 11 5259-5268. 13 DING WX YIN XM. Mitophagy mechanisms pathophysiological roles and analysis J. Biol Chem 2012 393 7 547-564. 14 ROMAO S MUNZ C. LC3-associated phagocytosis J. Autophagy 2014 10 3 526-528. 15 PANKIV S CLAUSEN TH LUMARK T et al. p62 /AQATM1 binds 24131-24145.
118 1. 1. 2 BALB /C 4 ~ 8 18 ~ 20 g 1 1. 1. 3 CO 2 SANYO 2014 71 830 65 000 OLYMPUS EYELA N-1100 26 270 24 SHB-Ⅲ S 040 2 LABCONCO LABCONCO Sigma4K15 3 Sigma TDL-5-A 1. 2 polysaccharides 10 1. 2. 1 EPS PDA 28 120 r /min 7 d 4 1 /3 3 NO 1. 2. 3 PBS CT26 2 10 6 /ml 12 K562 75% HL-60 SGC-7901 0. 2 ml / K562 SGC-7901 13 1. 2. 4 EPS 5-FU CT26 50 5-11 Trichoderma pseudokoningii Sevag = 4 1 V /V D101 EPS 1. 2. 2 CT26 TPS1-1 RPMI 1640 5% CO 2 37 CT26 5- BALB /C 5-FU 5-FU extracelluar polysaccharides of Trichoderma pseudokoningii 200 mg / kg d + 5-FU 20 mg / kg d 20 mg / kg d EPS 50 100 EPS CT26 10 d 12 h 8 5-FU 7 EPS + 5- FU 7 EPS + 5-FU 7 1 1. 1 95% EPS + 5-FU 7 75% 1. 1. 1 EPS CT26 0. 25% Gibco 5-FU = - Sigma RPMI 1640 / 100%
119 = mg / g = mg / g 1. 2. 5 EPS 5-FU FU 5-FU 12 h EPS 75% 5-FU 5-FU 5-5-FU CT26 1. 2. 6 EPS 5-FU 5-FU 12 h 5-FU EDTA EPS 200 mg / kg d 5-FU 1. 2. 7 ± 20 mg / kg d P < 0. 001 SPSS 11. 0 72. 24% EPS 5-FU CT26 Duunett-t P < 0. 05 2 5-FU 2 EPS 2. 1 EPS 5-FU CT26 1 1 CT26 x 珋 ± s / mg / kg d /g /g /% - 26. 39 ± 1. 34 2. 99 ± 0. 89-5-FU 20 18. 70 ± 1. 56 *** 1. 24 ± 0. 62 *** 58. 53 EPS + 5-FU 50 EPS + 20 5-FU 21. 72 ± 1. 86 ***# 1. 09 ± 0. 36 *** 63. 55 EPS + 5-FU 100 EPS + 20 5-FU 22. 89 ± 2. 51 **## 0. 89 ± 0. 51 *** 70. 23 EPS + 5-FU 200 EPS + 20 5-FU 23. 31 ± 2. 34 * ### 0. 83 ± 0. 49 *** 72. 24 F - 15. 096 16. 668 - P - < 0. 001 < 0. 001 - * P < 0. 05 **P < 0. 01 ***P < 0. 001 5-FU #P < 0. 05 ##P < 0. 01 ###P < 0. 001 2 CT26 x 珋 ± s / mg / kg d /g / mg /g /g / mg /g - 0. 209 ± 0. 069 7. 83 ± 2. 27 0. 129 ± 0. 024 4. 90 ± 0. 99 5-FU 20 0. 050 ± 0. 023 *** 2. 68 ± 1. 31 *** 0. 070 ± 0. 006 *** 3. 75 ± 0. 25 * EPS + 5-FU 50 EPS + 20 5-FU 0. 126 ± 0. 035 **## 5. 76 ± 1. 40 * ## 0. 116 ± 0. 031 ## 5. 27 ± 0. 99 ## EPS + 5-FU 100 EPS + 20 5-FU 0. 060 ± 0. 032 *** 2. 93 ± 1. 06 *** 0. 084 ± 0. 024 ** 3. 67 ± 0. 84 * EPS + 5-FU 200 EPS + 20 5-FU 0. 081 ± 0. 028 *** 3. 42 ± 0. 95 *** 0. 104 ± 0. 027 # 4. 43 ± 0. 90 F - 18. 19 17. 50 7. 073 4. 925 P - < 0. 001 < 0. 001 < 0. 001 0. 003 * P < 0. 05 **P < 0. 01 ***P < 0. 001 5-FU #P < 0. 05 ##P < 0. 01 2. 2 EPS 5-FU CT26 3 2. 3 EPS 5-FU CT26 5-FU 4 P < 0. 01 P < 0. 001 5-FU CT26 EPS 5-FU 5-FU 5-FU EPS 5-FU EPS 5-FU 5-FU P <
120 0. 01 5-FU EPS CT26 3 x 珋 ± s / mg / kg d /g /g /g - 0. 141 ± 0. 030 1. 325 ± 0. 177 0. 329 ± 0. 030 5-FU 20 0. 107 ± 0. 027 0. 931 ± 0. 218 ** 0. 237 ± 0. 034 *** EPS + 5-FU 50 EPS + 20 5-FU 0. 119 ± 0. 024 1. 189 ± 0. 210 0. 286 ± 0. 040 EPS + 5-FU 100 EPS + 20 5-FU 0. 116 ± 0. 029 1. 093 ± 0. 246 0. 279 ± 0. 043 EPS + 5-FU 200 EPS + 20 5-FU 0. 126 ± 0. 034 1. 013 ± 0. 202 * 0. 269 ± 0. 052 * F - 1. 476 3. 952 5. 074 P - 0. 233 0. 01 0. 003 * P < 0. 05 **P < 0. 01 ***P < 0. 001 4 x 珋 ± s / mg / kg d / 10 12 /L / 10 9 /L / 10 9 /L - 9. 33 ± 0. 73 3. 91 ± d1. 78 601. 00 ± d115. 56 5-FU 20 8. 85 ± 0. 24 2. 21 ± 1. 41 642. 57 ± 176. 53 EPS + 5-FU 50 EPS + 20 5-FU 8. 38 ± 1. 41 2. 37 ± 1. 34 418. 86 ± 81. 94 * ## EPS + 5-FU 100 EPS + 20 5-FU 9. 08 ± 0. 50 2. 82 ± 1. 03 454. 86 ± 122. 67 # EPS + 5-FU 200 EPS + 20 5-FU 8. 87 ± 0. 16 2. 96 ± 0. 80 568. 00 ± 108. 31 F - 1. 597 1. 895 4. 223 P - 0. 200 0. 136 0. 008 * P < 0. 05 5-FU #P < 0. 05 ##P < 0. 01 3 IL- 2 12 1969 18 14 5-FU 5-FU 15 5-FU EPS EPS 5-FU 16-17 5-FU 5-FU 12 K562 18 EPS 5-FU 5-FU
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