Abstract:Objective
To study the effect of intratumor injection of slowrelease 5FU on pancreatic carcinoma cells in nude mice,and on changes in serum tumor markers and cellular immunity of patients with pancreatic carcinoma.
Methods 1) In vitro experiments, the releasing action and antitumor effect of slowrelease 5FU were studied. Measurement of the concentration of effused fluid,calculation of amount of drug released,and observation of the inhibitory effects of effused fluid on PC3 strains of pancreatic cancer cellswere perfomed.(2) Human pancreatic carcinoma strain PC3 cells were cultured and inoculated into 60 nude mice,and were randomly divided into 5 groups according to various treatments received: NS injection as control group(A group), 5FU (10 mg/kg)IV injection group(B group), stroma implant group(C group), intratumor injection of high dose slowrelease 5FU (4mg/kg) group(D group) and intratumor injection of low dose slowrelease 5FU (1mg/kg) group(E group). Tumor size were measured before and 14 days after treatment. On week 2, histological changes of the tumors were examined. The apoptotic index (AI) of the tumor cells was detected by terminaldeoxynucleotide transferase mediated dUTP nick end labeling(TUNEL) and expression of bcl2 and Bax by immunohistochemistry.(3) 69 cases of unresectable pancreatic carcinoma were divided into 3 groups randomly:intratumor injection of slowrelease 5FU treated group(treatment group), intravenous injection of 5FU group(chemotherapy group), and control group. The serum values of CD3+, CD4+, CD8+, CD4+/ CD8+, NK cells, CEA, CA50, CA199, CA125 and CA242 were measured in all patients 1 day before and 14 days after operation.
Results 1) There was 0.85 mg 5FU released in the 1st day and 0.45 mg 5FU released in the 3rd day. The release remained constant at 0.25 mg and continued for about 14 days. (2) The tumor growth suppression rate on the 1st day by effusion fluid of slowrelease 5FU was 60.27% and on the 3rd day was 34.25%. Later, it remained at about 25.00%. The tumor growth rate was slower in D and E group than in other groups (P<0.05). The expression of bcl2 was markedly decreased but that of Bax remarked increased in D and E group than in the other groups (P<0.05). The extent of local inflammation and degree of thickness of blood vessel endothelium was more pronounced in D and E groups than in other groups (P<0.05).AI was significantly higher in D and E group than in other groups(P<0.05). In patients of intravenous injection of 5FU treated group, the serum levels of CD4+/ CD8+ and NK cells were much lower than in H patients of treatment group and the control group（P<0.05）;and the serum values of CEA, CA50, CA199, CA125 and CA242 in patients of treatment group were much lower than in patients the intravenous injection of 5FU group and the control group（P<0.05）.
Conclusions Slowrelease 5FU can constantly maintain drugrelease during 2 weeks of in vitro experment and has inhibitory action against human pancreatic cancer cell strain PC 3.Intratumor injection of slowrelease 5FU can inhibit the growth of pancreatic carcinoma by inducing local inflammation and thickening of blood vessel endothelium and upregulating apoptosis of pancreatic cancer cells. Intratumor embedding of slowrelease 5FU into the pancreatic cancer tissue of palients causes minimal damage of cellular immunity, but can decrease the serum values of CEA, CA50, CA199, CA125 and CA242, and might become an useful method for treating patients with unresectable pancreatic cancinoma.