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Increase in resistance to anticancer drugs involves occludin in spheroid culture model of lung adenocarcinoma A549 cells
https://gifu-pu.repo.nii.ac.jp/records/13466
https://gifu-pu.repo.nii.ac.jp/records/134665433d76f-0d8a-4570-9675-51292385d1df
| Item type | 研究室原著論文(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2019-03-05 | |||||
| タイトル | ||||||
| タイトル | Increase in resistance to anticancer drugs involves occludin in spheroid culture model of lung adenocarcinoma A549 cells | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| item_3_textarea_2 | ||||||
| 値 | Chemoresistance is a serious issue in the therapy of many cancers, but the molecular mechanism is little understood. The mRNA level of occludin (OCLN), a tight junctional protein, was increased in the cisplatin (CDDP), doxorubicin (DXR), 7-ethyl-10-hydroxy-camptothecin, or gemcitabine-resistant human lung adenocarcinoma A549 cells. Here, we investigated the regulatory mechanism and pathophysiological role of OCLN. OCLN was mainly localized at tight junctions in A549 and CDDP-resistant A549 (A549/CDDP) cells. The level of p-Akt in A549/CDDP cells was higher than that in A549 cells, and the mRNA and protein levels of OCLN were suppressed by a phosphoinositide 3-kinase (PI3K)/Akt pathway inhibitor, LY-294002, suggesting that a PI3K/Akt pathway is involved in the elevation of OCLN expression. The overexpression of OCLN in A549 cells decreased paracellular permeability to DXR. Cytotoxicity to CDDP was unaffected by OCLN-overexpression in 2D culture model. In 3D culture model, the spheroid size, hypoxic level, and cell viability were significantly elevated by CDDP resistance, but not by OCLN-overexpression. The accumulation inside the spheroids and toxicity of DXR were correlated with OCLN expression. Our data suggest that OCLN is not directly involved in the chemoresistance, but it enhances chemoresistance mediated by suppression of accumulation of anticancer drugs inside the spheroids. | |||||
| bibliographic_information |
en : Scientific Reports 巻 8, 号 1, p. 15157--, ページ数 -, 発行日 2018 |
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| item_3_text_4 | ||||||
| 値 | 10.1038/s41598-018-33566-w | |||||
