Effect of Fluorouracil Combined With Harmine on Induction of Apoptosis in Apoptosis Induction in Pancreatic Cancer Cells (AsPC-1) and the Expression of Apoptotic Genes (BAX, P53, Caspase-3, and Caspase-9)

Abstract

Objective: Pancreatic cancer is one of the deadliest cancers related to 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. In this study, the effect of harmine combined with fluorouracil on apoptosis induction in pancreatic cancer cells (AsPC-1) and the expression of apoptotic genes was investigated. Methods: In this experimental study, MTT assay was used to study the cytotoxic effects. Annexin V/propidium iodide test and DAPI staining method were used to determine the type of cell death. The expression of apoptotic genes (P53, Bax, Caspase-3, and Caspase-9) was measured by real-time PCR. The data were analyzed using one-way ANOVA in SPSS software, version 16. The significance level was set at 0.05. Results: The results of MTT assay showed that the use of harmine at 20 μg/mL concentration combined with 10 μg/mL fluorouracil significantly reduced the growth (IC50) of AsPC-1 cells. The results of DAPI staining and annexin V/propidium iodide test showed the 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: The combined use of harmine and fluorouracil can induce apoptosis in pancreatic cancer cells due to high cytotoxicity and reduce the concentration of chemotherapy drugs. Therefore, this method can be used along with other treatment methods for pancreatic cancer.