Activator protein 1 promotes gemcitabine-induced apoptosis in pancreatic cancer by upregulating its downstream target Bim

Abstract

Abstract. Gemcitabine is a commonly used chemotherapy drug in pancreatic cancer. The function of activator protein 1 (AP-1) is cell-specific, and its function depends on the expression of other complex members. In the present study, we added gemcitabine to the media of Panc-1 and SW1990 cells at clinically achieved concentrations (10 µM). Compared with constitutive c-Fos expression, c-Jun expression increased in a dose-dependent manner upon gemcitabine treatment. c-Jun overexpression increased gemcitabine-induced apoptosis through Bim activation, while cell apoptosis and Bim expression decreased following c-Jun knockdown. Furthermore, gemcitabine-induced apoptosis and Bim levels decreased when c-Jun phosphorylation was blocked by SP600125. Our findings suggest that c-Jun, which is a member of the AP-1 complex, functions in gemcitabine-induced apoptosis by regulating its downstream target Bim in pancreatic cancer cells.

lncRNA RP11-147L13.8 suppresses metastasis and chemo-resistance by modulating the phosphorylation of c-Jun protein in GBC

“…Previously, several studies reported that c-Jun protein played an important role in inducing the drug resistance of gemcitabine resistance, including breast cancer, pancreatic cancer, and bladder cancer. 32 , 33 , 34 , 35 All these studies further supported our findings. This suggested that the combinatorial use of gemcitabine and RP11-147L13.8 transcriptional promoters might produce better therapeutic effects for advanced-stage GBC patients, which shed new insights into the clinical treatment for GBC patients.…”

Identification of key pharmacological components and targets for Aidi injection in the treatment of pancreatic cancer by UPLC-MS, network pharmacology, and in vivo experiments

“…However, the function of AP-1 appears to be cell-specific, and its biological function depends on the expression of members of the AP-1 complex. As reported, gemcitabine significantly increased the expression of JUN in Panc-1 cells [ 38 ].…”

The Olive Biophenols Oleuropein and Hydroxytyrosol Selectively Reduce Proliferation, Influence the Cell Cycle, and Induce Apoptosis in Pancreatic Cancer Cells

“…JUN and FOS are known proto-oncogenes which dimerize to form the transcription factor AP-1. More specifically, forced expression of c-Jun and c-Fos has previously been linked to the induction of apoptosis in pancreatic cancer cells in vitro [ 33 ]. In the present study ( Table 2 ), the expression of JUN significantly increased 4.6-fold after oleuropein treatment ( p = 0.000126) and 4.7-fold after hydroxytyrosol treatment ( p = 0.000041).…”

“…Additionally, treatment of myelodysplastic cells with the plant-derived compound, withaferin A, caused an increase in the mRNA expression of JUN and FOS and their subsequent protein expression and resulted in downstream activation of apoptosis [ 49 ]. More specifically, Ren et al [ 33 ] were able to show that increasing the expression of c-Jun and c-Fos in MIA PaCa-2 cells caused the downstream induction of apoptosis via activation of Bim and the subsequent effect on Bcl-2 family proteins. These previous studies support the theory that the induction of apoptosis in this study could be due to an increased expression of c-Jun and c-Fos, which dimerize into AP-1 and result in activation of the AP-1/JNK pathway.…”