A molecular targeting against nuclear factor‐ κ B, as a chemotherapeutic approach for human malignant mesothelioma
| Autor: | Noriko Okamoto, Akane Tanaka, Ginae Ahn, Saori Ishizaka, Hiroshi Matsuda, Yosuke Amagai, Hyosun Jang, Kumiko Oida, Akira Matsuda, Sho Nishikawa, Kyungsook Jung |
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| Rok vydání: | 2014 |
| Předmět: |
Mesothelioma
Cancer Research Pathology medicine.medical_specialty Guanine Lung Neoplasms Cell cycle checkpoint Antineoplastic Agents Inflammation Mice SCID Pemetrexed Biology NF-κB Malignant transformation Mice Glutamates Cell Line Tumor medicine Animals Humans Animal model Radiology Nuclear Medicine and imaging Molecular Targeted Therapy Cyclin D3 Original Research Cell Proliferation Mice Inbred BALB C Cell growth Mesothelioma Malignant NF-kappa B Cell Cycle Checkpoints Cell cycle medicine.disease Xenograft Model Antitumor Assays Oncology Cell culture Benzamides Cancer research cell cycle Female medicine.symptom |
| Zdroj: | Cancer Medicine |
| ISSN: | 2045-7634 |
| DOI: | 10.1002/cam4.202 |
| Popis: | Chronic inflammation due to the absorption of asbestos is an important cause of mesothelioma. Although the increased prevalence of mesothelioma is a serious problem, the development of effective chemotherapeutic agents remains incomplete. As the nuclear factor-κB (NF-κB) pathway contributes to malignant transformation of various types of cells, we explored NF-κB activity in three different pathological types of malignant mesothelioma cells, and evaluated the therapeutic potential of a recently reported NF-κB inhibitor, IMD-0354. NF-κB was constantly activated in MSTO-211H, NCI-H28, and NCI-H2052 cells, and the proliferation of these cell lines was inhibited by IMD-0354. D-type cyclins were effectively suppressed in mixed tissue type MSTO-211H, leading to cell cycle arrest at sub G1 /G1 phase. IMD-0354 reduced cyclin D3 in both epithelial tissue type NCI-H28 and sarcomatoid tissue type NCI-H2052. In a sphere formation assay, IMD-0354 effectively decreased the number and diameter of MSTO-211H spheres. Preincubation of MSTO-211H cells with IMD-0354 delayed tumor formation in transplanted immunodeficient mice. Furthermore, administration of IMD-0354 markedly rescued the survival rate of mice that received intrathoracic injections of MSTO-211H cells. These results indicate that a targeted drug against NF-κB might have therapeutic efficacy in the treatment of human malignant mesothelioma. |
| Databáze: | OpenAIRE |
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