Induction Of Pancreatic Carcinoma In C₅₇BL/6 Rats Following Exposure To DMBA And The Inhibitory Effect Of Elemene On The Tumor Cells In Vitro

Pancreatic carcinoma is one of the highest malignant tumors of digestive system. Pancreatic carcinoma occurs with a higher incidence in our country. The prognosis for patients with pancreatic carcinoma is extremely poor, because of the unavailability of early diagnosis and against chemotherapy. The early symptoms of pancreatic carcinoma are usually vague, atypical. Overall, the 5-year survival rate is less than 1%, and cures are extremely rare. Most patients die in less than 1 year. The median length of survival for patients with unresectable tumors is less than 6 months. Even for those few patients with resectable tumors, results of surgery are not good. Only about 3~5% of patients who undergo resection will live 5 years. The poor prognosis is due in part to the difficulty in making a diagnosis while the tumor is at an early stage: Only about 10% of pancreatic carcinomas are resectable at the time of diagnosis. To study its biological characteristics, the efficient methods for early diagnosis and treatments, it is necessary to develop a model of pancreatic carcinoma in rats. P53 is an important gene. In the present study, there was overexpression of P53 in pancreatic adenocarcinoma in human, which suggested that P53 mutations may play a sustained role in the pathogenesis of pancreatic adenocarcinoma. If we can develop a model of pancreatic carcinoma in rats, which have the same gene mutations with human. It will be very useful. Objective To study the pathogenesis of pancreatic carcinoma and investigate the p53 genes expression in carcinogenesis and development of pancreatic carcinoma induced by DMBA; And study the cytostatic effect of elemene emulsion on the tumor cell. Methods High dose (10mg/100gweight) of dimethylbenzanthracene (DMBA) was put into the parenchyma of rat pancreas to develop a model of pancreatic carcinoma in rat. Immunohistochemical SP method was used to study the expression of P53 in pancreatic carcinoma induced by DMBA in rats. The MTT assay was applied to determine the values OD of the formazan produced of tumor cell after exposing to different concentrations of the drug. Results The prevalence of pancreatic carcinoma among DMBA-treated rats within 3-5 months was 30%(12/40). Among the 12 rats with pancreatic cancer, 3 rats developed pancreatic ductal adenocarcinomas with glandular duct-like distribution of cancer cells, various sizes of glandular cavities, obvious nucleiheterotpic and atypical cocus of cancer cells under a microscope. And the remaining 9 cases were diagnosed having pancreatic fibrosarcoma with a great number of fibrosarcoma cells substituting for pancreas. There was no expression of P53 in normal pancreatic tissues. The overexpression of P53 was detected in pancreatic carcinoma (10/12). The expression of P53 protein was associated with histological grading. The results showed that elemene emulsion had significant cytostatic or cytocidal effect on the pancreatic cancer cell, and represented dose-time response relationship. IC50 of the elemene emulsion were 35.6mg/l in 24h and 29.38mg/l in 48h. Conclusion High dose DMBA was put into the parenchyma of rat pancreas could obtained a pancreatic cancer model with high incidence in a short time. There are P53 protein overexpressions in the pancreatic carcinoma induced by DMBA in rats. P53 may participate in the course ofthe carcinogenesis of pancreatic carcinoma in rats, and P53 protein overexpression may relate to the degree of malignancy of the tumors. The elemene emulsion had good proliferation inhibition effect on the pancreatic cancer cell, and represented dose-time response relationship.