BackgroundOur previous study has demonstrated that knockdown of activated ERK1/2(pERK1/2) sensitizes pancreatic cancer cells to chemotherapeutic drug gemcitabine (Gem) treatment. However, the details of this survival mechanism remain undefined. It has also shown that Bcl-2 confers resistance and Bax sensitizes to gemcitabine-induced apoptosis in pancreatic cancer cells. Furthermore, the extracellular signaling-regulated kinase (ERK) signaling pathway regulates Bcl-2/Bax expression ratio. We therefore tested the hypothesis that pancreatic cancer cells are resistant to gemcitabine and this resistance is due to activation of ERK1/2 and subsequent upregulation of Bcl-2 and downregulation of Bax.MethodsPancreatic cancer cell BXPC-3 was used in the study. The effect of pharmacological inhibition of ERK1/2 on resistance of pancreatic cancer cells to apoptosis induced by treatment with gemcitabine was analyzed. The following methods were utilized: TUNEL and ELISA were used to detect apoptosis. Western blot was used to detect the protein expression.ResultsGemcitabine treatment enhanced the activity of ERK1/2 in the BXPC-3 cells. Inhibition of the ERK1/2 by PD98059 could downregulate Bcl-2 and upregulate Bax and was associated with restoration of sensitivity to gemcitabine in BXPC-3 cells. Depletion of endogenous Bcl-2 expression by specific small interfering RNA transfection significantly increased gemcitabine-induced cell apoptosis. Combined treatment with PD98059 and Bax siRNA transfection could decrease gemcitabine-induced ERK1/2 and Bax activation, which subsequently resulted in decreased apoptosis.ConclusionsThe upregulation of ERK1/2-dependent Bcl-2 and downregulation of ERK1/2-dependent Bax can protect human pancreatic cancer cells from gemcitabine-induced apoptosis. Targeting the ERK1/2-Bax/Bcl-2 pathway may in part lead to sensitization of pancreatic cancer to gemcitabine.
Abstract. The present study aimed to determine the expression levels and biological functions of in patients with esophageal squamous cell carcinoma (ESCC). A total of 60 patients with ESCC and 30 healthy individuals were enrolled and reverse transcription-quantitative polymerase chain reaction was performed to measure the expression levels of miR-202. In order to investigate the effects of miR-202 expression levels on the proliferative, migratory and invasive abilities of ESCC cells, methylthiazolyl-tetrazolium bromide proliferation, in vitro scratch and Transwell ® chamber assays were performed. Expression levels of miR-202 were significantly decreased in the peripheral blood of patients with ESCC, which is associated with the degree of cell differentiation and lymph node metastasis (P<0.05). Following miR-202 transfection, cell proliferation was significantly inhibited (P<0.05). Cell migration and invasion was also significantly inhibited by miR-202 transfection (P<0.05). The results of the present study demonstrated that the expression of miR-202 inhibited the proliferation, migration and invasion of ESCC cells. Furthermore, low expression levels of miR-202 were detected in the peripheral blood of patients with ESCC, which is associated with the development, invasion and metastasis of ESCC.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.