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Insulin-induced Enhancement Of Anticancer Response To 5-Fu In Human Colon Cancer HCT-8 And Esophageal Cancer Eca-109 Cell Lines

Posted on:2005-01-02Degree:MasterType:Thesis
Country:ChinaCandidate:W MaFull Text:PDF
GTID:2144360125957786Subject:Oncology
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The malignant tumor has badly been threatening the health and life of human beings. At present, chemotherapy is one of the main ways to the treatment of cancer. But the chemotherapeutic drugs have so much toxicity that it kills normal cells as well as tumor cells. What's more, tumors are not sensitive to the chemotherapeutic drugs or have a drug resistance which usually makes the chemotherapy fail. Now, it is urgent to find potentiators which can improve the cancer treatment by making the chemotherapeutic drugs kill cancer cells more effectively and decrease the damnification to normal cells. It's an urgent problem to settle in clinical oncology and cancer comprehensive treatment.During the clinical practice, people have found that rapidly growing tumors are often responsive to chemotherapy, whereas slowly growing tumors respond less favorably to chemotherapy. One reason is that the cells in rapidly growing tumors have better metabolism and are subject to be attacked, whereas the cells in slowly growing tumors have a lower metabolism level and are not easy to be attacked. So, can we improve the chemotherapeutic effect after increasing the tumor metabolic level?Insulin is a metabolism accelerant. Its prominent function is to promote the tissue incepting more glucose and to promote complex metabolism in liver, muscle and fat. Investigations show that insulin can increase the metabolic level of normal cell and malignant cells.We use 5-Fliorouracil (5-Fu), a chemotherapeutic drug, after modificating caner cell with insulin and observe whether the insulin can induce an enhancement of chemotherapeutic response of 5-Fliorouracil to HCT-8 human colon cancer cell and Eca-109 human esophageal cancer cell. Material and method:(1) Eca-109 human esophageal cancer cell line and HCT-8 human colon cancer cell line were chosen as the trial material with 5-Fliorouracil as a chemotherapeutic drug and insulin as a metabolism accelerant. Esophageal carcinoma tissue and normal Esophagus tissue were obtained from Pathology Department of the Second Affiliated Hospitol of Zhengzhou University. (2)MTT assay was used to examine the suppressive rate of cell growth dealt with different drugs. (3) Cell cycle and cell metabolism were examined by PI fluorescence flow cytometry. (4)The expression of cyclinD protein in Eca-109 cell before and after affected by insulin were tested by immunocytochemistry. (5)The expression of insulin-like growth factors-1 receptor (IGF-1R) on malignant and normal esophagus tissue were tested by immunohistochemistry. (6)A11 experimental data were processed by statistical package for social and sicence 10.0(SPSS 10.0). There was a statistical significant when PO.05 occurred. Results:(1) 5-Fliorouracil with different concentration act on two cancer cell line. Select the concentration of 5-Fliorouracil with 50% inhibitory rate as the experimental concentration. Namely, the concentration of 5-Fliorouracil act on HCT-8 cell line was 10 u g/ml and on Eca-109 cell line was 50 u g/ml.(2) To find the best inducement time of insulin, the inhibitory rates of different time groups were tested including the 24h, 12h, 8h, 4h, Oh before 5-Fu and the 4h, 8h after 5-Fu time groups. Statistical results of three times test showed, for both cancer cells, the inhibitory rates of the former 8h, 4h and Oh groups were significant higher than that of 5-Fu control groups in three times test(P<0.01). Other time groups were no significant with 5-Fu control groups(P>0.05), further more, some groups were even lower than 5-Fu control groups. The OD numerical value ofinsulin control group were higher than that of vacant control group with a significant difference (P<0.05). It showed that insulin can induce a faint proliferation of cancer cell.(3) To find the best inducement concentration of insulin, the inhibitory rates of different concentration groups were tested including 0.08mu/ml, 0.8mu/ml, 1.6mu/ml, 8mu/ml, 16mu/ml, 80mu/ml, 160mu/ml, 200mu/ml groups. Statistical results of three times test showed, fo...
Keywords/Search Tags:Insulin, Tumor, Chemotherapeutic sensitivity
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