Mitomycin Slow-release Seeds For Treating Pancreatic Cancer In Nude Mice Experimental Models

Background Pancreatic cancer is one of the most common digestive system tumors with high malignancy and poor prognosis.In recent years,the global morbidity has increased significantly.Due to the biological and pathological features of pancreatic cancer,early stages lack specific symptoms,early diagnosis is difficult,most patients are already in the advanced stage when diagnosed,and more patients with adjacent organs and distant metastases,the surgical resection rate is very low,the five-year survival rate was only about 20 percent,even for patients who received radical surgery.Systemic intravenous chemotherapy is still the main treatment for clinical pancreatic cancer.However,pancreatic cancer is a tumor lack of blood supply,when systemic chemotherapy is used,the dose of drugs that can reach tumor lesions is very small.Increasing the dose of chemotherapy drugs will increase the serious systemic side effects caused by chemotherapy drugs,such as nausea,vomiting,loss of appetite,bone marrow suppression,etc.;patients often have to stop treatment because of the difficulty of tolerating chemotherapy.In recent years,great progress has been made with slow release administration.The so-called interstitial chemotherapy is a combination of a chemotherapeutic drug and a specific carrier.It is implanted into the tumor by ultrasound,CT and other imaging techniques.The carrier is slowly degraded in the human body,and the chemotherapy drug is slowly released for a long time.The action time is long,and the chemotherapeutic drug forms a higher therapeutic concentration in the tumor,which increases the therapeutic effect and reduces the systemic side effects at the same time.Studies on interstitial chemotherapy for pancreatic cancer show thatinterstitial chemotherapy can effectively control the growth of pancreatic cancer cells and reduce the adverse reactions of chemotherapy drugs.Objective In this study,we established a model of pancreatic cancer in nude mice,mixed specific carriers with mitomycin drugs to produce mitomycin slow-release particles,implanted the mitomycin slow-release particles into subcutaneous tumor formation of pancreatic cancer in nude mice,and analyzed the efficacy and safety of mitomycin slow-release particles in the treatment of pancreatic cancer,provides an experimental basis for the clinical application of EUS guided interstitial chemotherapy in pancreatic cancer.Method 1.SW1990 pancreatic cancer cell lines were cultured in the laboratory,and then planted subcutaneously under the skin of Balb/c-nu nude mice.The tumor size was observed and measured regularly,after about 3 weeks,a subcutaneous tumor model of pancreatic cancer in nude mice was successfully established and the tumor volume was recorded.2.Twenty-four tumor-forming BALB/C nude mice,16-20 g,were randomly divided into four groups.particle group(injection of mitomycin chemotherapeutic particles 0.39mg/only),injection group(injection of mitomycin for injection into the tumor,Mitomycin dose as same as particle group),matrix group(in vivo implanted with a matrix of 0.31 mg / only),control group(intratumoral injection of normal saline 0.1 ml / only).3.The length,width,and thickness of the tumor were measured before and after administration on the 3rd,6th,9th,12 th and 14 th days,and the tumor volume was calculated to draw the tumor growth curve.At the same time,the changes in the body mass and mental state of mice in each group were observed and recorded.4.Two weeks later,all the experimental nude mouse models were sacrificed,the intact tumors were removed and weighed,and the tumor inhibition rate of each group was calculated.5.HE staining of tumors was performed to observe thepathological differences of tumor cells in nude mice.6.The concentration of mitomycin in the tumors of nude mice in the particle group and the injection group was detected by high performance liquid chromatography.Results The model of pancreatic cancer model in nude mice was successfully established.Compared with the matrix group and the control group,the volume of the tumor in the particle group and the injection group was significantly lower than that in the matrix group and the control group(P<0.05).Compared with the injection group,the volume of the tumor in the particle group was significantly lower than that in the injection group(P<0.05).Compared with the injection group,the toxic reaction of the gastrointestinal tract of the nude mice in the particle group was short and the symptoms were mild(P<0.05).The results of pathological examination showed that the particle group and the injection group showed a large amount of necrosis of pancreatic cancer cells compared with the matrix group and the control group(P<0.05).Compared with the injection group,the necrotic area of cancer cells increased in the particle group,and the difference was statistically significant(P<0.05).High performance liquid chromatography(HPLC)showed that the concentration of mitomycin in the tumor of nude mice in the particle group was(0.76�0.41)ng/m L,while the concentration of mitomycin in the tumor of injection group was lower than the detection limit,the difference between the two groups was statistically significant(P <0.05).Conclusion Mitomycin slow-release particles can significantly inhibit the growth of pancreatic cancer xenografts in nude mice,increase the local drug concentration and reduce systemic toxicity.The application of mitomycin slow-release particles in the treatment of pancreatic cancer xenografts is safe and effective.