Effect of dibutyryl cyclic AMP on the cell cycle of human pancreatic cancer inoculated in nude mice

Abstract

The prognosis of pancreatic cancer is very poor because of its high malignant potential. To improve the prognosis of pancreatic cancer, a decrease in the grade of malignancy by dibutyryl cyclic AMP (db-cAMP), a differentiation inducer, was attempted using human pancreatic cancer cell line inoculated to nude mice. In this study, 0.1 or 5.0 mumol/animal/day of db-cAMP was administered for 7 consecutive days in short-term group animals and for 28 consecutive days in long-term group animals. Animals in both groups are sacrificed 28 days after first administration of db-cAMP, and tumor size, histology, and cell cycle analysis using flow cytometry (FCM) were studied. Tumor size and histology showed no significant changes by db-cAMP. However, in cell cycle analysis, 5.0 mumol/animal/day of db-cAMP brought significant block of the cell cycle phases between G1 and S in the short-term group and the phase between S and G2/M in the long-term group, indicating a decrease in cell cycle speed and, consequently, a decrease in the proliferation of tumor cell. The results show that db-cAMP may be useful in decreasing the grade of malignancy of pancreatic cancer.