The Development And Progression Of Colon Adenoma With Relationship Between Cyclooxygenase-2,5-lipoxygenase

Objective: To explore the relationship between cyclooxygenase-2,5-lipoxygenase and the development and progression of colorectal adenoma and Whether there is a dynamic relationship between the two,to provide a new theoretical basis for targeted therapy of colorectal eoplasms.Methods: Fifty-five SD rats were randomly divided into 5 groups,10 in every intervention group which were DMH + Celecoxib group,DMH + Zileuton group,DMH +Celecoxib + Zileuton group,15 in the DMH group and 10 in the control group.DMH +Celecoxib group was given intraperitoneal injection of dimethylhydrazine(20mg / kg)once a week and fed with Celecoxib inhibitor(Celecoxib 50 mg / kg)every other day.DMH + Zileuton group was given intraperitoneal injection of dimethylhydrazine(20mg /kg)once a week and fed with Zileuton inhibitor(zileuton 50 mg / kg)every other day.The DMH + Celecoxib + Zileuton group was given intraperitoneal injection of dimethylhydrazine(20mg / kg)once a week and fed with Celecoxib inhibitor(Celecoxib25mg / kg)+ Zileuton inhibitor(zileuton 25 mg / kg)every other day.The rats in the DMH group were treated with dimethylhydrazine(20mg/kg)intraperitoneally once a week and fed with the same amount of saline every other day;the same amount of normal saline was given to the control group.18 weeks,20 weeks,22 weeks 3 batches of rats.HE staining to understand the model construction.The expressions of PGE2 and LTB4 in colorectal tissues were detected by enzyme-linked immunosorbent assay.The expression of Ki-67 in colorectal tissues was detected by immunohistochemistry.The expression of COX-2 m RNA and 5-LOX m RNA in colorectal tissues was detected by real-time PCR.Results:(1)The tumor formation rate of colorectal tumor in experimental group and intervention group was 64.3%.No colorectal tumor were found in the control group.(2)The results of RT-PCR showed that the expression level COX-2/5-LOX m RNA in control group was significantly lower than DMH + Celecoxib group,DMH + Zileuton group,DMH + Celecoxib + Zileuton group and DMH group(P <0.05).The expression level of COX-2/5-LOX m RNA in DMH group was significantly higher than in DMH + Celecoxib group,DMH + Zileuton group,DMH + Celecoxib + Zileuton group and control group(P<0.05).The expression level of COX-2 m RNA in Zileuton group was significantly higher than in DMH + Celecoxib group,DMH + Celecoxib + Zileuton group(P <0.05).The expression level of COX-2 m RNA in DMH + Celecoxib + Zileuton group was a little higher than in DMH + Celecoxib group(P> 0.05).The expression level of 5-LOX m RNA in DMH + Celecoxib group was significantly higher than in DMH + Zileuton group and DMH + Celecoxib + Zileuton group(P <0.05),The expression level 5-LOX m RNA in DMH + Zileuton group was a little higher than DMH + Celecoxib + Zileuton group,the difference was not statistically significant(P> 0.05).(3)ELISA was used to detect PGE2 /LTB4.The results showed that PGE2 / LTB4 was expressed in colorectal tissues,and the contents of PGE2 / LTB4 in colorectal tissues were compared.The results showed that the content of PGE2 / LTB4 in DMH + Zileuton group DMH + Celecoxib group,DMH +Celecoxib + Zileuton group and DMH group were significantly higher than in control group(P <0.05).The content of PGE2 / LTB4 in DMH group was significantly higher than in DMH + Celecoxib group,DMH + Zileuton group and DMH + Celecoxib + Zileuton group(P <0.05).The content of PGE2 in DMH + Zileuton group was significantly higher than that in DMH + Celecoxib group and DMH + Celecoxib + Zileuton group(P<0.05),The content of PGE2 in DMH + Celecoxib group was a little higher than that in DMH + Celecoxib + Zileuton group(P> 0.05).The content of LTB4 in DMH + Celecoxib group was higher than that in DMH + Zileuton group and DMH + Celecoxib + Zileuton group(P <0.05).The content of LTB4 in DMH + Zileuton group was a little higher than that in DMH + Celecoxib + Zileuton group(P> 0.05).(3)Immunohistochemistry was used to detect the expression of Ki-67 Positive rate,the control group,DMH + Celecoxib +Zileuton group,DMH + Celecoxib group,DMH + Zileuton group and DMH group were respectively 16.67%(2/12),31.3%(5/16),40.0%(6/15),50.0%(9/18),77.78%(35/45),the expression of Ki-67 Positive rate in DMH group was significantly higher than in DMH + Celecoxib + Zileuton group,DMH + Celecoxib group,DMH + Zileuton group,the difference was statistically significant(P <0.05).Conclusion: 1.COX-2,5-LOX and its downstream product PEG2,LTB4 in expression level of colorectal adenoma-adenocarcinoma were gradually increased.2.The COX-2/5-LOX inhibitors can reduce expression level of COX-2/5-LOX m RNA and PGE2/ LTB4,inhibit colorectal cell proliferation and inhibit colorectal adenoma-adenocarcinoma development trend.3.There is some synergy between the COX-2/5-LOX pathways.