Effects of hexahydrocurcumin in combination with 5-fluorouracil on dimethylhydrazine-induced colon cancer in rats  

作　　者：Khanitta Srimuangwong Chainarong Tocharus Jiraporn Tocharus Apichart Suksamrarn Pornphorm Yoysungnoen Chintana 

机构地区：[1]Department of Anatomy,Faculty of Medical Science,Naresuan University,Phitsanulok 65000,Thailand [2]Department of Anatomy,Faculty of Medicine,Chiang Mai University,Chiang Mai 50200,Thailand [3]Department of Physiology,Faculty of Medicine,Chiang Mai University,Chiang Mai 50200,Thailand [4]Department of Chemistry,Faculty of Science,Ramkhamhaeng University,Bangkok 10240,Thailand [5]Division of Physiology,Faculty of Medicine,Thammasat University,Rangsit Campus,Pathumthani 12120,Thailand

出　　处：《World Journal of Gastroenterology》2012年第47期6951-6959,共9页世界胃肠病学杂志（英文版）

基　　金：Supported by National Research Council of Thailand;Partial Support from the Strategic Basic Research Grant of the Thailand Research Fund,No.MRG5180092

摘　　要：AIM:To investigate the effects of hexahydrocurcumin(HHC),and its combination with 5-fluorouracil(5-FU) on dimethylhydrazine(DMH)-induced colon cancer in rats.METHODS:Male Wistar rats weighing 100-120 g were used as subject models.Aberrant crypt foci(ACF),early preneoplastic lesions of colon cancer,were induced by subcutaneous injection of DHM(40 mg/kg) twice a week for two weeks.After the first DMH injection,rats were treated daily with vehicle(n = 12),curcumin(CUR)(50 mg/kg)(n = 12),HHC(50 mg/kg) orally(n = 12),and treated weekly with an intraperitoneal injection of 5-FU(50 mg/kg)(n = 12),or a combination of 5-FU plus CUR(n = 12) and HHC(n = 12) at the same dosage(s) for 16 wk.The total number of ACF and large ACF were assessed.Cyclooxygenase(COX)-1 and COX-2 expression were detected by immunohistochemistry in colon tissues.The quantitative data of both COX-1 and COX-2 expression were presented as the percentage of number of positive-stained cells to the total number of cells counted.Apoptotic cells in colon tissues were also visualized using the dUTP-biotin nick end labeling method.Apoptotic index(AI) was determined as the percentage of labeled nuclei with respect to the total number of nuclei counted.RESULTS:The total number of ACF was highest in the DMH-vehicle group(1558.20 ± 17.37),however,the number of ACF was significantly reduced by all treatments,5-FU(1231.20 ± 25.62 vs 1558.20 ± 17.37,P < 0.001),CUR(1284.20 ± 25.47 vs 1558.20 ± 17.37,P < 0.001),HHC(1086.80 ± 53.47 vs 1558.20 ± 17.37,P < 0.001),DMH-5-FU + CUR(880.20 ± 13.67 vs 1558.20 ± 17.37,P < 0.001) and DMH-5-FU + HHC(665.80 ± 16.64 vs 1558.20 ± 17.37,P < 0.001).Interestingly,the total number of ACF in the combined treatment groups,the DMH-5-FU + CUR group(880.20 ± 13.67 vs 1231.20 ± 25.62,P < 0.001;880.20 ± 13.67 vs 1284.20 ± 25.47,P < 0.001) and the DMH-5-FU + HHC group(665.80 ± 16.64 vs 1231.20 ± 25.62,P < 0.001;665.80 ± 16.64 vs 1086.80 ± 53.47,P < 0.001) were significantly reduced as compared to 5-FU or each treatment alone.LAIM：To investigate the effects of hexahydrocurcumin（HHC）,and its combination with 5-fluorouracil（5-FU） on dimethylhydrazine（DMH）-induced colon cancer in rats.METHODS：Male Wistar rats weighing 100-120 g were used as subject models.Aberrant crypt foci（ACF）,early preneoplastic lesions of colon cancer,were induced by subcutaneous injection of DHM（40 mg/kg） twice a week for two weeks.After the first DMH injection,rats were treated daily with vehicle（n = 12）,curcumin（CUR）（50 mg/kg）（n = 12）,HHC（50 mg/kg） orally（n = 12）,and treated weekly with an intraperitoneal injection of 5-FU（50 mg/kg）（n = 12）,or a combination of 5-FU plus CUR（n = 12） and HHC（n = 12） at the same dosage（s） for 16 wk.The total number of ACF and large ACF were assessed.Cyclooxygenase（COX）-1 and COX-2 expression were detected by immunohistochemistry in colon tissues.The quantitative data of both COX-1 and COX-2 expression were presented as the percentage of number of positive-stained cells to the total number of cells counted.Apoptotic cells in colon tissues were also visualized using the dUTP-biotin nick end labeling method.Apoptotic index（AI） was determined as the percentage of labeled nuclei with respect to the total number of nuclei counted.RESULTS：The total number of ACF was highest in the DMH-vehicle group（1558.20 ± 17.37）,however,the number of ACF was significantly reduced by all treatments,5-FU（1231.20 ± 25.62 vs 1558.20 ± 17.37,P 0.001）,CUR（1284.20 ± 25.47 vs 1558.20 ± 17.37,P 0.001）,HHC（1086.80 ± 53.47 vs 1558.20 ± 17.37,P 0.001）,DMH-5-FU ＋ CUR（880.20 ± 13.67 vs 1558.20 ± 17.37,P 0.001） and DMH-5-FU ＋ HHC（665.80 ± 16.64 vs 1558.20 ± 17.37,P 0.001）.Interestingly,the total number of ACF in the combined treatment groups,the DMH-5-FU ＋ CUR group（880.20 ± 13.67 vs 1231.20 ± 25.62,P 0.001;880.20 ± 13.67 vs 1284.20 ± 25.47,P 0.001） and the DMH-5-FU ＋ HHC group（665.80 ± 16.64 vs 1231.20 ± 25.62,P 0.001;665.80 ± 16.64 vs

关 键 词：Hexahydrocurcumin Curcumin analog Colon cancer Combination treatment CYCLOOXYGENASE-2 Apoptosis 

分 类 号：R735.35[医药卫生—肿瘤]