Abstract
In this study, we investigated the mechanisms by which the chemotherapeutic agent paclitaxel (PTX) induced the expression of B7-H1 immunosuppressive molecules in the human colorectal adenocarcinoma cell line SW480 and the hepatocellular carcinoma cell line HepG2. We found ptX induced B7-H1 protein expression in SW480 and HepG2 cells as demonstrated by immunofluorescence and flow cytometry and mRNA expression by using real-time quantitative polymerase chain reaction (PCR). Moreover, PTX treatment induced Erk½ phosphorylation in both cell lines. PTX-increased B7-H1 mRNA expression was significantly blocked by MEK inhibitor U0126. However, the protein expression caused by PTX was only partially blocked by U0126. Our results suggest that PTX upregulated B7-H1 expression in cultured SW480 and HepG2 cells via both transcriptional and post-transcriptional mechanisms. This may help us better understand PTX-related tumor immune evasion.
MeSH terms
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Adenocarcinoma / drug therapy*
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Adenocarcinoma / metabolism*
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Adenocarcinoma / pathology
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Antineoplastic Agents, Phytogenic / pharmacology*
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B7-H1 Antigen / genetics
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B7-H1 Antigen / metabolism*
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Carcinoma, Hepatocellular / drug therapy
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Carcinoma, Hepatocellular / metabolism
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Carcinoma, Hepatocellular / pathology
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Cell Line, Tumor
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Colorectal Neoplasms / drug therapy
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Colorectal Neoplasms / metabolism
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Colorectal Neoplasms / pathology
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Gene Expression Regulation, Neoplastic / drug effects
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Humans
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Liver Neoplasms / drug therapy
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Liver Neoplasms / metabolism
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Liver Neoplasms / pathology
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MAP Kinase Signaling System / drug effects*
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism
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Paclitaxel / pharmacology*
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Phosphorylation / drug effects
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Protein Kinase Inhibitors / pharmacology
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Protein Processing, Post-Translational / drug effects
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RNA, Messenger / metabolism
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Real-Time Polymerase Chain Reaction
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Reverse Transcriptase Polymerase Chain Reaction
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Time Factors
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Up-Regulation / drug effects*
Substances
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Antineoplastic Agents, Phytogenic
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B7-H1 Antigen
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CD274 protein, human
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Neoplasm Proteins
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Protein Kinase Inhibitors
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RNA, Messenger
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Paclitaxel