Investigation To The Cytotoxity Of Irinotecan (CPT-11) To Lung Cancer Cells, Prediction Method Of Curative Effect And The Activation Of Carboxylesterase Isoenzymes To Irinotecan

Lung cancer is one of the serious diseases that endanger the healthness of mankind. The synthesis therapy is the standard mode in which chemical drugs play an important role. CPT-11, which is activated to SN-38 in vivo by carboxylesterase, has extensive antineoplastic spectrum and shows prospective effects on gastrointestinal tumors, lung cancers and et al.We conduct a series of trials as followings to study the antineoplastic mechanism of CPT-11 and the cytotoxic difference of CPT-11 to different kinds of human lung cancer cells, to found the examination methods which will be effective to the CPT-11 purposive therapy, to extract the human hepatocyte carboxylesterase-1 and carboxylesterase-2 and analyze their cytotoxicity to human lung cancer cells in order to improve the efficiency of CPT-11 activation.Trial I:Examining the IC50 of CPT-11 and SN-38 to 2 kinds of small-cell lung cancer cells and 4 kinds of non-small cell lung cancer cells(including the DDP-resisted A549/DDP cell line) by the MMT method.We found that the IC50 of CPT-11 to non-small cell lung cancer cell lines were higher than that to the small cell lung cancer cell lines. The CPT-11 resistances of A549 cell line(including the DDP-resisted A549/DDP cell line) were higher than that of others, there were statistic difference(p＜0.05＝. There were no statistic difference in the SN-38 sensitivity(p＞0.05). There were no statistic difference in small cell lung cancer group and the non-small cell lung cancer group under the SN-38 action(p＞0.05).Trial II:Using the immunohistochemical method to deal with 70 cases of human lung cancer tissues and 46 cases human normal lung tissues and examining the expression of human hepatocyte carboxylesterase.As far as the expression of human hepatocyte carboxylesterase be concerned, there were 17 cases in the squamous cell type and the positive rate was 48.6%, 12 positive cases in the adenocarcinoma type and the positive rate was 52.2%, 9 positive cases in the small cell type and the positive rate was 75.0%. In all 58 cases of non-small cell lung cancer, 29 cases were positive and the positive rate was 50.0%.The positive rate of small cell lung cancers was higher than that of the non-small cell lung cancers but had no statistic difference(p＞0.05). There were 13 cases positive in the all 25 cases of stage Ⅰ lung cancer, the positive rate was 50.0%. There were 15 cases positive and 10 cases positive in theⅡand Ⅲ stage respectively, the positive rate were 57.7% and 52.6% respectively. There was no statistic difference in these 3 groups by the X2 test(p＞0.05).In 25 cases of squamous cell carcinoma and 15 cases of adenocarcinoma and 6 cases of small cell lung cancer that the topoisomeraseI activites were examined ,the carboxylesterase positive rate were 52.0%, 53.3% and 66.7% respectively. The topoisomeraseI activity of 40 cases non-small cell lung cancer were 22311±6832u/mg protein and the topoisomeraseI activities of 6 cases non-small cell lung cancer were 22532±7132u/mg protein. There was no statistic difference between them(p＞0.05). The topoisomeraseI activities of normal lung tissues and lung cancer tissues were 15210±6380u/mg protein and 22351±6582u/mg protein. There was significant statistic difference(p＜0.05＝. In all 46 cases of lung cancer, there were 25 cases positive and 21 cases negative in the expression of human hepatocyte carboxylesterase. The topoisomeraseI activities in the two groups had no statistic difference(p＞0.05). The statistic analysis of topoisomeraseI activities of different stages showed no statistic difference(p＞0.05).Trial III: Using the biochemical methods to extract the topoisomeraseI and determine their activities. Using the biochemical methods of gel filtration,iron-exchange and the to hemogenize the human hepatocyte and get the hCE-1 and hCE-2. The IC50 measurement by MMT methods was used to evaluate the CPT-11 cytotoxicity influnced by hCE-1 and hCE-2 respectively. In this trial the hCE-1 and hCE-2 were got by the biochemical methods as above and dem...