Administration of Gapmer-type Antisense Oligonucleotides Targeting γ-Glutamylcyclotransferase Suppresses the Growth of A549 Lung Cancer Xenografts
| Autor: | HIROMI II, YUUYA KASAHARA, HARUMI YAMAGUMA, SUSUMU KAGEYAMA, AKIHIRO KAWAUCHI, SATOSHI OBIKA, SUSUMU NAKATA |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Cancer Research Lung Neoplasms Antineoplastic Agents Apoptosis Cell Cycle Proteins General Medicine Mice SCID Oligonucleotides Antisense Xenograft Model Antitumor Assays Tumor Burden Gene Expression Regulation Neoplastic Oncology A549 Cells Caspases Animals Humans Cycloheximide gamma-Glutamylcyclotransferase Cell Proliferation Signal Transduction |
| Zdroj: | Anticancer research. 42(3) |
| ISSN: | 1791-7530 |
| Popis: | γ-Glutamyl cyclotransferase (GGCT) is up-regulated in various cancer types, including lung cancer. In this study, we evaluated efficacy of gapmer-type antisense oligonucleotides (ASOs) targeting GGCT in an A549 lung cancer xenograft mouse model and studied their mechanisms of action.GGCT was inhibited using GGCT-ASOs and cell proliferation was evaluated by dye exclusion test. Western blot analysis was conducted to measure expression of GGCT, p21, p16 and p27, phosphorylation of AMP-activated protein kinase, and caspase activation in A549 cells. Induction of apoptosis and up-regulation of reactive oxygen species were assessed by flow cytometry using annexin V staining and 2',7'-dichlorodihydrofluorescein diacetate dye, respectively.GGCT-ASOs suppressed GGCT expression in A549 cells, inhibited proliferation, and induced apoptosis with activation of caspases. GGCT-ASOs also increased expression of cell-cycle regulating proteins, phospho-AMPK and ROS levels. Systemic administration of GGCT-ASOs to animals bearing A549 lung cancer xenografts showed significant antitumor effects without evident toxicity.GGCT-ASOs appear to be promising as novel cancer therapeutic agents. |
| Databáze: | OpenAIRE |
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