Synergistic Effect of Fluorouracil Combined With Harmin on Induction of Apoptosis in Aspc-1 Cell Line And The Expression of Apoptotic Genes (Bax, P53 And Caspase3 &9)

Introduction: Pancreatic cancer is one of the deadliest cancers of the digestive system in the world. Due to the increasing resistance of cancer cells to chemotherapy and its side effects, there is a need for drugs with fewer side effects and natural origin. Methods: In this study, the effect of harmine and its concomitant use with fluorouracil to induce apoptosis in pancreatic cancer cells, AsPC-1 cell line, was investigated. MTT method was used to study the cytotoxic effects Annexin V/PI test and DAPI staining methods were used to determine the type of cell death. The expression of apoptotic genes, P53, Bax, Caspase-3, and Caspase-9, were measured by Real time-PCR. Results: The results of MTT method showed that the use of harmine at 20 μg/ml concentration combined with fluorouracil at 10 μg/ml decreased the growth of AsPC-1. The results of DAPI staining and anxin test also showed induction of apoptosis in treated samples. In addition, the results of real-time PCR showed that the expression of BAX, P53, Caspase 3 and Caspase 9 genes increased in the treated groups compared to the control group. Conclusion: Based on the results, concomitant use of harmine and fluorouracil can induce apoptosis in pancreatic cancer cells due to its high cytotoxicity and can reduce the concentration of chemotherapy drugs. Therefore, it can is used in combination with other cancer treatments.