ABSTRACT
BACKGROUND/AIM: Anti-inflammatory drugs, such as aspirin, have attracted attention as anticancer agents that can be applied to standard chemotherapy for pancreatic cancer. This study aimed to examine the antitumour effects and possible fundamental mechanisms of aspirin in pancreatic cancer cells. MATERIALS AND METHODS: We appraised the antitumour effects of aspirin on cell proliferation and tumour growth, cell cycle distribution, apoptosis, signalling pathways, angiogenesis-related proteins, and phosphorylated receptor tyrosine kinases (p-RTKs) and identify miRNAs associated with its antitumour effects. RESULTS: Aspirin inhibited cell proliferation in pancreatic cancer cell lines and induced G0/G1 cell cycle arrest by decreasing the expression of cyclin D1. Aspirin inactivated glycogen synthase kinase (GSK)-3ß but had no effect on the p38 mitogen-activated protein kinase (MAPK) pathway, p-RTKs, or angiogenesis-related molecules. Aspirin treatment statistically increased the expression of 274 miRNAs in PANC-1 cells and 30 miRNAs in PK-8 cells and suppressed the expression of 294 miRNAs in PANC-1 cells and 13 miRNAs in PK-8 cells. CONCLUSION: Aspirin inhibited the proliferation of pancreatic cancer cells and induced cell cycle arrest. Aspirin also inactivated GSK-3ß but not the p38 MAPK pathway. Thus, aspirin may be used in combination with chemotherapeutic agents for pancreatic cancer.
Subject(s)
Adenocarcinoma , Antineoplastic Agents , MicroRNAs , Pancreatic Neoplasms , Adenocarcinoma/drug therapy , Adenocarcinoma/genetics , Antineoplastic Agents/pharmacology , Apoptosis , Aspirin/pharmacology , Cell Cycle Checkpoints , Cell Line, Tumor , Cell Proliferation , Glycogen Synthase Kinase 3 beta/genetics , Glycogen Synthase Kinase 3 beta/metabolism , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/pathology , Phosphorylation , p38 Mitogen-Activated Protein Kinases/metabolism , Pancreatic NeoplasmsABSTRACT
BACKGROUND/AIM: Drug resistance to molecular targeted agents, such as lenvatinib, is an important issue. The aim of this study was to explore the mechanism of lenvatinib resistance and to investigate potential drugs that may improve the treatment of lenvatinib-resistant (LR) hepatocellular carcinoma (HCC). MATERIALS AND METHODS: LR cells were developed by long-term culture under lenvatinib exposure. We analyzed the biological characteristics of LR cells in vitro, and investigated the antitumor effects and endogenous mechanisms of cisplatin in LR cells. RESULTS: The proliferative potential of LR cells was enhanced by activation of ERK signaling and changes in several miRNAs. Cisplatin inhibited cell proliferation of LR cells and induced G2/M cell cycle arrest. Furthermore, cisplatin triggered the DNA damage response, via the ATM/ATR-Chk1/Chk2 signaling pathway. CONCLUSION: Proliferation of LR cells was induced upon ERK signaling activation. Cisplatin exerted antitumor effects in LR cells and was involved in the regulation of miRNAs associated with drug resistance.
Subject(s)
Antineoplastic Agents/pharmacology , Carcinoma, Hepatocellular/drug therapy , Cisplatin/pharmacology , Drug Resistance, Neoplasm , Liver Neoplasms/drug therapy , Phenylurea Compounds/pharmacology , Protein Kinase Inhibitors/pharmacology , Quinolines/pharmacology , Animals , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Cell Proliferation/drug effects , Female , G2 Phase Cell Cycle Checkpoints/drug effects , Gene Expression Regulation, Neoplastic , Humans , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Mice, Inbred BALB C , Mice, Nude , MicroRNAs/genetics , MicroRNAs/metabolism , Signal Transduction , Tumor Burden , Xenograft Model Antitumor AssaysABSTRACT
BACKGROUND/AIM: The promoter region of the telomerase reverse transcriptase (TERT) gene is a regulatory element capable of affecting TERT expression, telomerase activity, and telomerase length. Mutations within the TERT promoter region are the most common mutations in many cancers. In this study, we characterized the TERT promoter mutation status in hepatobiliary, pancreatic, and gastrointestinal cancer cell lines. MATERIALS AND METHODS: TERT promoter mutation status was assessed by digital PCR in 12 liver cancer, 5 cholangiocarcinoma (CCA), 12 pancreatic cancer, 17 gastrointestinal cancer, and 3 healthy control cell lines. RESULTS: The C228T promoter mutation was detected in 9 liver cancer lines, and the C250T TERT mutation was detected in 1 oesophageal squamous cell carcinoma line. CONCLUSION: The C228T promoter mutation is specific to liver cancer cell lines among various gastrointestinal cancer cell lines. These data will contribute to future research on the tumorigenic mechanisms and clinical use of digital PCR to detect mutations.