Studies On The Chemopreventive Effects Of Jiangchasu In Rat Colorectal Carcinogenesis Induced By DMH

Background/ObjectivesJiangchasu is composed of curcumin and catechins, both of which are naturally plant active components and have nearly no adverse effects. It has been proved that both curcumin and catechins posses widespread anticancer properties. Now aberrant crypt foli (ACF) has been proposed as a good intermediate biomarker in colorectal cancer. Cyclooxygenase 2 (COX-2) and peroxisome proliferator-activated receptor gamma (PPARy) have emerged as promising candidate molecular targets for colorectal cancer. The thesis aimed to evaluate whether a combination of curcumin and catechins shows synergistic effects for cancer-preventive activity for rat colorectal cancer induced by dimethylhydrazine (DMH). It is focused on questions as follows.1. To observe the inhibition effects of Jiangchasu on the number ofcolon ACF and colorectal cancer induced by DMH on Wistar rats.2. To evaluate the effects of Jiangchasu, curcumin and catechins on the cell proliferation and apoptosis of rat colorectal cancer were investigated, which was helpful to elucidate the anticancer mechanism of Jiangchasu.3. To detect the effects of Jiangchasu, curcumin and catechins on expression of COX-2 and PPARy in DMH induced rat colorectal cancer, hoping to elucidate the chemoprevention mechanisms of Jiangchasu in molecular levels.MethodsI. Wistar rat colorectal cancer was induced by DMH. All rats were randomly divided into five groups: (1) negative group: standardized food. (2) DMH group: standardized food + DMH. (3) curcumin group: standardized food with 0.2% curcumin + DMH. (4) catechins group: standardized food with 0.2% catechins + DMH. (5) Jiangchasu group: standardized food with 0.2% (curcumin and catechins) + DMH. The number of rat colorectal ACFs was observed by methylene blue staining. The incidence, number and size ofcolorectal cancer were accounted. The changes of rat colorectal tissues in morphology were observed through hematoxylin-eosin (HE) staining.2. Proliferation index displayed by PCNA through immunohischemistry and apoptosis index revealed by TUNEL are used to evaluate the chemoprevention effects of curcumin, catechins and Jiangchasu in rat colorectal cancer induced by DMH .3. The expression of COX-2 and PPAR y in tissues of rats colorectal mucosa at 12W and in tissues of rats colorectal cancer at 32W after first DMH administration were examined with immunohistochemical staining, RT-PCR and Western blotting methods.Results1. The effects of Jiangchasu on the number of ACF At 12 weeks after the first administration, rats belong to groups 2-5 developed ACF. The dietary administration of Jiangchasu, curcumin and catechins caused significantly inhibition in the ACF incidence than that of in DMH treatment group (P<0.01). The inhibition effect of Jiangchasu group was the highest among three chemopreventive groups (P<0.05). There was no difference between curcumin and catechins group.2. The effects of Jiangchasu on colorectal cancer At 32 weeks after the first administration, the incidence of the colorectal cancer were 81.15%, 61.11%, 58.82% and 38.89% in DMH, curcumin, catechins and Jiangchasu group respectively. The incidence of colorectal cancer in Jiangchasu group was significantly lower than that of in DMH group (P<0.05). The average numbers and volumes of rumors were significantly decreased in Jiangchasu group than that of in curcumin or cathchins group administration alone. All preventive drugs had no effects on the differentiation of cancer.3. The effects of Jiangchasu on cell proliferation index and apoptosis index Compared with DMH group, proliferation index in preventive group was markedly decreased and apoptosis index was obviously increased. The effects of Jiangchasu group were significantly higher than that of the other groups.4. The effects of Jiangchasu on expression of COX-2 DMH couldinduce the expression of COX-2 in colon mucosa tissues at 12W and in colorectal cancer tissues at 32W. The results of RT-PCR showed...