Calpain-2 inhibitor treatment preferentially reduces tumor progression for human colon cancer cells expressing highest levels of this enzyme
| Autor: | Michael P. Marciel, David Horio, Verena Martinez, Aaron H. Rose, Ann S. Hashimoto, Peter R. Hoffmann, FuKun W. Hoffmann, Pietro Bertino |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Cancer Research Programmed cell death Colorectal cancer medicine.medical_treatment Cell Down-Regulation Mice Nude colorectal cancer Antineoplastic Agents Apoptosis intestinal cancer Mice 03 medical and health sciences inflammatory bowel disease In vivo medicine Animals Humans Radiology Nuclear Medicine and imaging Original Research Cancer Biology Cell Nucleus Chemotherapy Calpain Chemistry NF-kappa B protease HCT116 Cells medicine.disease Survival Analysis Xenograft Model Antitumor Assays 3. Good health Treatment Outcome 030104 developmental biology medicine.anatomical_structure Oncology Cell culture Tumor progression Colonic Neoplasms Disease Progression Calpain-2 Cancer research Calcium |
| Zdroj: | Cancer Medicine |
| ISSN: | 2045-7634 |
| DOI: | 10.1002/cam4.1260 |
| Popis: | Calpain‐2 levels are higher in colorectal tumors resistant to chemotherapy and previous work showed calpain‐2 inhibitor therapy reduced inflammation‐driven colorectal cancer, but direct effects of the inhibitor on colon cancer cells themselves were not demonstrated. In the present study, five human colon cancer cell lines were directly treated with a calpain‐2 inhibitor and results showed increased cell death in 4 of 5 cell lines and decreased anchorage‐independent growth for all cell five lines. When tested for levels of calpain‐2, three cell lines exhibited increasing levels of this enzyme: HCT15 (low), HCC2998 (medium), and HCT116 (significantly higher). This was consistent with gel shift assays showing that calpain‐2 inhibitor reduced of NF‐κB nuclear translocation most effectively in HCT116 cells. Ability of calpain‐2 inhibitor to impede tumor progression in vivo was evaluated using intrarectal transplant of luciferase‐expressing cells for these three cell lines. Results showed that calpain‐2 inhibitor therapy reduced tumor growth and increased survival only in mice injected with HCT116 cells. These data suggest calpain‐2 inhibitor treatment may be most effective on colorectal tumors expressing highest levels of calpain‐2. |
| Databáze: | OpenAIRE |
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