Experimental Study On Growth Inhibitory Effect Of Chemotherapeutic Drugs Including Fliorouracil, Cisplatin, Epirubicin, Mitomycin And P21 McAB On The Pancreatic Cancer Cell Line--Aspc-1 And Bxpc-3

Objective: 1. To study the growth inhibitory effect of chemotherapeutic drugs on the pancreatic cancer cell line(cell 1.) ?Aspc-1 and Bxpc-3, and that related to the varied concentration and exposed time of chemotherapeutic drugs administrated singly or combinatively.2. To study the the growth inhibitory effect and inducing apoptosis function of p21 McAB directly and combination used with 5 - FU, E-ADM?DDP and MMC.3. To observe the interaction of 5-fluorouracil ,cisplatin and epirubicin on human pancreatic carcinoma cell line Aspc-1.Materials and Methods: 1. Four chemotherapeutic drugs including 5-FU, E-ADM, MMC and DDP, were administrated singly or combinatively and used with varied concentration (dl?d2?d3 and d4) and exposed time (24? 48 and 72 hours) .Then the growth inhibitory effect on two cell 1. resulting from these drugs was assayed by MTT colorimetry and analysised by analysis of variance.2. The MTT assay and Flow cytometry(FCM) were used to observe the growth inhibitory and inducing apoptosis effect on two cell 1. resulting from p21 McAB directly and combination used with 5 - FU, E-ADM?DDP and MMC. The singnificant difference was test used t-test.3. The MTT assay and median-effect principle were used to observe theinteraction of 5-fluorouracil ,cisplatin and epirubicin on human pancreatic carcinoma cell line Aspc-1.Results: l.The growth inhibitory rate between the two cell lines was significantly different when singly or combinatively used( singly used F = 111.0 P0.001, combinatively used F 4.5 P =0.034), and it also increased with the increment of drug and/or the prolongation of exposed time (Concentration F17018 PO.001 ) (time F=8461 PO.001 ) . A significant difference was observed among the different drugs or between the cells(singly used F=470 PO.001, combinatively used F=136 PO.001).2. The p21 McAB had direct anti-tumor effect and could increase the each of the four kinds of chemotherapy agents. FCM results revealed that p21 McAB had function of directly inducing apoptosis of two cell lines and combination use of p21 McAB and 5-FU or E-ADM could increased the apoptosis rate in these two lines..3. The interaction between 5-FU and DDP was synergistic at lower concentration (CI<1) and antagonistic at higher concentration (CI>).The interactions between 5-FU and E-ADM ,DDP and E-ADM were both sligh antagonisticConclusion: The results indicated that the chemotherapeutic efficiency of pancreatic carcinoma cell lines?Aspc-1 and Bxpc-3 can be improved by increment of the local drug concentration and prolongation of the exposed time by intraarterial infusion or consecutive arterial infusion through the reserved catheter. Pancreatic carcinoma has high expression of K-ras gene products p21 protein. P21 McAB has direct anti-tumor effect on pancreatic adenocarcinoma and can improve its result when applied in combination with chemotherapy drugs. These results that p21 McAB might be an ideal carrier for radioimmunolocalization and immunotherapy of human pancreatic adenocarcinoma. On celline Aspc-1, the interactions between 5-fluorouracil and epirubicin ,cisplatin and epirubicin were both sligh antagonistic, which of5-fluorouracil and cisplatin was related with the drugs concentration but it was antagonistic at most concentration. The antagonistic between the drugs is a hinderance in the chemotherapy of pancreatic carcinoma.