論文 - 詳細
| RRC ID | 78173 |
|---|---|
| 著者 | Tamura S, Tazawa H, Hori N, Li Y, Yamada M, Kikuchi S, Kuroda S, Urata Y, Kagawa S, Fujiwara T. |
| タイトル | p53-armed oncolytic adenovirus induces autophagy and apoptosis in KRAS and BRAF-mutant colorectal cancer cells. |
| ジャーナル | PLoS One |
| Abstract |
Colorectal cancer (CRC) cells harboring KRAS or BRAF mutations show a more-malignant phenotype than cells with wild-type KRAS and BRAF. KRAS/BRAF-wild-type CRCs are sensitive to epidermal growth factor receptor (EGFR)-targeting agents, whereas KRAS/BRAF-mutant CRCs are resistant due to constitutive activation of the EGFR-downstream KRAS/BRAF signaling pathway. Novel therapeutic strategies to treat KRAS/BRAF mutant CRC cells are thus needed. We recently demonstrated that the telomerase-specific replication-competent oncolytic adenoviruses OBP-301 and p53-armed OBP-702 exhibit therapeutic potential against KRAS-mutant human pancreatic cancer cells. In this study, we evaluated the therapeutic potential of OBP-301 and OBP-702 against human CRC cells with differing KRAS/BRAF status. Human CRC cells with wild-type KRAS/BRAF (SW48, Colo320DM, CACO-2), mutant KRAS (DLD-1, SW620, HCT116), and mutant BRAF (RKO, HT29, COLO205) were used in this study. The antitumor effect of OBP-301 and OBP-702 against CRC cells was analyzed using the XTT assay. Virus-mediated modulation of apoptosis, autophagy, and the EGFR-MEK-ERK and AKT-mTOR signaling pathways was analyzed by Western blotting. Wild-type and KRAS-mutant CRC cells were sensitive to OBP-301 and OBP-702, whereas BRAF-mutant CRC cells were sensitive to OBP-702 but resistant to OBP-301. Western blot analysis demonstrated that OBP-301 induced autophagy and that OBP-702 induced autophagy and apoptosis in human CRC cells. In BRAF-mutant CRC cells, OBP-301 and OBP-702 suppressed the expression of EGFR, MEK, ERK, and AKT proteins, whereas mTOR expression was suppressed only by OBP-702. Our results suggest that p53-armed oncolytic virotherapy is a viable therapeutic option for treating KRAS/BRAF-mutant CRC cells via induction of autophagy and apoptosis. |
| 巻・号 | 18(11) |
| ページ | e0294491 |
| 公開日 | 2023-1-1 |
| DOI | 10.1371/journal.pone.0294491 |
| PII | PONE-D-23-29831 |
| PMID | 37972012 |
| PMC | PMC10653454 |
| MeSH | Adenoviridae / genetics Adenoviridae / metabolism Apoptosis / genetics Autophagy / genetics Caco-2 Cells Cell Line, Tumor Colorectal Neoplasms* / drug therapy Colorectal Neoplasms* / therapy ErbB Receptors / genetics ErbB Receptors / metabolism Humans Mitogen-Activated Protein Kinase Kinases / metabolism Mutation Proto-Oncogene Proteins B-raf* / genetics Proto-Oncogene Proteins B-raf* / metabolism Proto-Oncogene Proteins c-akt / metabolism Proto-Oncogene Proteins p21(ras) / genetics Proto-Oncogene Proteins p21(ras) / metabolism TOR Serine-Threonine Kinases / metabolism Tumor Suppressor Protein p53 / genetics Tumor Suppressor Protein p53 / metabolism |
| IF | 2.74 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 9 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | CACO-2(RCB0988) COLO205(RCB2127) |