| Adenocarcinoma of the pancreas is one of the most common cause resulted in deaths by cancer in China and the Western World. The incidence of adeno-carcinoma of the pancreas has steadily risen over the past 4 decades. Pancreatic cancer ranks continuously as the fourth major reason of death caused by cancer in China. Although significant progress has been made in the surgical treatment of this malignancy, most pancreatic cancer patients are diagnosed at an advanced stage, and because of the lack of effective therapies, the prognosis of such patients is extremely poor. Despite advances in our understanding of the molecular biology of pancreatic cancer, the systemic treatment of this disease remains unsatisfactory. For many years, 5 - fluorouracil has been the standard chemotherapeutic drug used in the treatment of pancreatic cancer, and more recently gemcitabine has shown promising potential and is widely used in developed countries. However, response rates fail to exceed 20% even with combination therapy. The dismal prognosis of this disease makes it an appropriate model for evaluation of new, alternative therapies such as treatment with differentiating agents like retinoids and vitamin D analogues.Studies of the anti - tumor actions of retinoids and Vitamin D derivatives show that growth inhibition, cellular differentiation and /or apoptosis can be induced in a variety of cell types. Many clinic researches show that because the effects of most retinoids used in clinical trials are reversible, patients should be treated for prolonged periods of time. Side effects of retinoids limit their use to short - term periods. Another, retinoid resistance has been identified in the treatment of a variety of malignant cells. It has been concerned how to decrease side effects of retinoids and vitamin D analogues and to produce synergistic effects by combination of them. Recent investigations have shown that retinoids together with Vitamin D analogues induce additive or synergistic growth inhibi-tion in myeloma cells, Leukemia cells and breast cancer cells. In pancreatic cancer, a few similar situations have been reported and the mechanism should be investigated.ObjectiveThe purpose of this study is to determine anti - proliferative effects of aroti-noid Ro40-8757 together with EB1089 on human pancreatic cancer cell line JF-305 and to find a new method of therapy of pancreatic cancer by combination of retinoids and vitamin D analogues. The basis of theory and experiment to decrease toxic effects and to inhibit retinoid resistance will be established in phase HI clinical trials.Methods1. Materials1. 1 CompoundsRo40-8757 was provided by Roche Company. The compound was dissolved in DMSO and reached a concentration of 1 x 10 ~ mol/L. The solution was stored at -70 .EB1089 was provided by Leo Pharmaceutical Products. The compound was dissolved in ethanol and stored in dark at - 20T;. Dilutions was made up in DMSO and RPMI 1640.1. 2 Cell cultureThe human pancreatic cancer cell line JF-305 was received from Tumor Institute, Chinese Medical University. Cell line was cultivated in RPMI 1640 medium supplemented with 10% fetal bovine serum (FBS) and antibiotics at 37 Tl in a humidified atmosphere of 5%CO2.2. MethodsIn our research, MTT assay was used to determine growth - inhibitory rate of Ro40-8757, EB1089 and Ro40-8757 together with EB1089 on human pancreatic cancer cell line JF-305. By means of statistical analysis, the growth - inhib- 鈥?itory effects of Ro40-8757 and EB1089 and synergistic effects in combination of the two compounds will be studied. The possibility of Ro40-8757 together with EB1089 in therapy of pancreatic cancer will be probed.ResultsThese results suggest that Ro40-8757 and EB1089 have an obvious growth -inhibitory effects on cell line JF-305. The growth of cell line JF-305 was inhibited by EB1089 in a dose -dependent fashion. The maximal inhibitory rates of Ro40-8757 and EB1089 on human pancreatic cancer cell line JF-305 were 49.67% and 56. 11% aft... |
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