Neoadjuvant Chemotherapy-induced Apoptosis Of Colon Cancer Cells And Mechanisms

Backgrounds: It had been proved that apoptosis of tumor cells induced by chemotherapeutic agents was one of important mechanism for treatment of anti-tumor.The good effects have been acquired by treatment of advanced colon carcinoma with project of hydroxycamptothecin combined with 5-fluorouracil and calcium Folinate, namely project of HFCF, in clinic implying. But there are rarely experimental reports which study on molecular mechanism of the neo-adjuvant chemotherapy-induced apoptosis in colon Carcinoma cells .Objective: To probe the probable molecular mechanism of the neoadjuvant chemotherapy-induced apoptosis in colon Carcinoma by project of hydroxycamptothecin combined with 5-Fluorouracil and calcium Folinate.Methods: HCPT lomg/dl~5^ 5-Fu SOOmg/d^s, and CF 200mg/di~5 were administered intravenously in cases of 20 patients before operation. The specimens were obtained during operation. The change of biochemistry and caspase-3 activity in apoptotic cells were evaluated by DNA electrophoresis and colorimetric assay respectively. The expressions of I K B a mRNA and TRAF-5 mRNA were detected by semiquatitative technique of RT-PCR. These results were compared with those of non-chemotherapy group and paratumor tissue group each other.Results: (1) The significant apperence of apoptotic DNA ladder could be observed by DNA electrophoresis in the Neoadjuvant chemotherapy group, while the non-chemotherapy group was not obvious. (2)The caspase-3 activity was significant higher in the group of neo-adjuvant chemotherapy than in the groups of non-chemotherapy and praratumor tissue, difference -s were statistically significant (P < 0.05); (3) There were higher expression of TRAF-5 mRNA (P < 0.05) and trend of lower expression of I K B a mRNA(P > 0.05) in colon carcinoma tissue respectively. But, after chemotherapy-induced by project of HFCF, expression of TRAF-5 mRNA and expression of I K B a mRNA wereinobvious down-regulation(P < 0.05) and up-regulation(p <0.05) respectively in colon carcinoma tissue.Conclusion: The TRAF-5 mRNA was high expresion in colon cancer, which indicted that TRAF-5 mRNA played certain role in process of colon cancer occurring; Neo-adjuvant Chemotherapy-induced apoptosis of colon carcinoma cells by project of HCPT combined with 5-Fu and CF might be correlation with down-regulation of TRAF-5 mRNA expression and up-regulation of I K B a mRNA expression and activation of caspase-3 activity.