The Expression Of COX-2, HMLH1 And HMSH2 In Colorectal Cancer And The Effects Of NSAIDs On Gastric Carcinoma Cells And Colonic Carcinoma Cells

Objective 1 To investigate the expression of COX-2,hMLH1 and hMSH2 in colorectal cancer.2 To observe the effects of three kinds of non-steroidal anti-inflammatory drugs(NSAIDs): COX-2 non-selective inhibitor-aspirin, indomethacin and COX-2 selective inhibitor NS-398 on human gastric adenocarcinoma cell lines MKN-45,SNU-1 and human colonic adenocarcinoma cell line LS-174-T.Material and methods1 The expression of COX-2,hMLH1 and hMSH2 in colorectal cancer1.1 Material:78 cases surgically resected colorectal carcinoma were used.Among them,58 cases were adenocarcinoma ,13 cases were mucinous adenocarcinoma,and 7 cases were signet-ring cell carcinoma.6 cases of normal colorectal mucosa were selected as control. 1.2 The expression of COX-2, hMLH1 and hMSH2 was detected in the normal colonic mucosa tissue and the colorectal carcinoma tissue with immunohistochemistry staining. 1.3 Statistical analysis :Chi-Square test was used to test the discrepancy of COX-2,hMLH1,hMSH2 expression in the patients of different histological types , with or not with lymph node metastasis and membrane invasion ,and different gender by using SAS software.P<0.05 was considered statistically significant.2 Culture of gastric and colonic cellsThe effects of NSAIDs on MKN-45 and LS-174-T cells' growth were determined by using MTT assay.The activity changes of SNU-1 induced by drugs were observed by trypan blue staining.Apoptosis rate induced by drugs was detected by using flow cytometry(FCM). HE staining was performed on cell climing slices,and to observe the morphologic changes of cells.Ultrastructure changes of cells treated by drugs were observed by transmission electron microscopy(TEM) and scanning electron microscopy(SEM) .Statistical analysis was performed by using the two sample Student's-t test and analysis of variance.P<0.05 was considered statistically significant.Results1 The expression of COX-2,hMLH1 and hMSH2 in colorectal carcinoma1.1 The results of immunohistochemistry stainingThere were positive expression of hMLH1 and hMSH2 in normal colon mucosa,while no COX-2 expression.The positive expression rate of COX-2 in colorectal carcinoma was 74.36%(58/78).The negative expression rates of hMLH1 and hMSH2 in colorectal carcinoma were 29.49%(23/78), 28.21%(22/78) respectively.1.2 The expression of COX-2, hMLH1 and hMSH2 with clinical pathology characters Significant difference between the level of COX-2 expression and lymph node metastasis was found, in the groups of with and not with lymph node metastasis, the rate of high COX-2 expression in the former group was higher than the latter one, and had statistical significance, P<0.05.Further testing demonstrated that COX-2 expression and with or not with lymph node metastasis had completely positive correlation in colorectal carcinoma,rs>0;hypothesis testing of rs demomstrated that P<0.01. No significant discrepancy was found between the level of COX-2 expression and diffenent gender,diffenent histological types and with or not with serous membrane invasion,P>0.05 evenly.Significant difference between the level of hMLH1 expression and histological types was found, the rate of high hMLH1 expression was the highest in adenocarcinoma,and the lowest in mucinous adenocarcinoma,P<0.05. No significant difference was found between the level of hMLH1 expression and different gender, with or not with lymph node metastasis and serous membrane invasion,P>0.05 evenly. No significant difference was found between the level of hMSH2 expression and different gender, different histological types and wether or not with lymph node metastasis and serous membrane invasion,P>0.05 evenly.2 The effects of NSAIDs on human gastric adenocarcinoma cell lines MKN-45,SNU-1 and human colonic adenocar- cinoma cell line LS-174-T2.1 The effects of NSAIDs on cells' growthNSAIDs inhibited the growth of the above three cell lines,and with time and dosage dependence.In the same cell line,the lowest concentration of NS-398 was needed to get the same inhibit...