Growth inhibitory effect of the Src inhibitor dasatinib in combination with anticancer agents on uterine cervical adenocarcinoma cells

• Material Type: 博士論文
• Title: Growth inhibitory effect of the Src inhibitor dasatinib in combination with anticancer agents on uterine cervical adenocarcinoma cells
• Author/Editor: Takiguchi, Eri; Nishimura, Masato; Mineda, Ayuka; Kawakita, Takako; Abe, Akiko; Irahara, Minoru
• Author Heading: Takiguchi, Eri; Nishimura, Masato; Mineda, Ayuka; Kawakita, Takako; Abe, Akiko; Irahara, Minoru
• Publication, Distribution, etc.: Spandidos Publications
• Publication Date: 2017-08-28
• Publication Date (W3CDTF): 2017-08-28
• Alternative Title: 子宮頸部腺癌細胞においてSrc阻害薬ダサチニブを抗癌剤と併用したときの増殖抑制効果; GROWTH INHIBITORY EFFECT OF DASATINIB COMBINED WITH ANTICANCER AGENTS
• Periodical title: Experimental and Therapeutic Medicine
• No. or year of volume/issue: 14 5
• Volume: 14
• Issue: 5
• Pages: 4293-4299
• ISSN (Periodical Title): ISSN : 1792-0981; ISSN : 1792-1015
• Degree grantor/type: 徳島大学
• Date Granted: 2018-01-25
• Dissertation Number: 甲第3121号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: Src; dasatinib; paclitaxel; oxaliplatin; cervical adenocarcinoma
• Target Audience: 一般
• Note (General): Uterine cervical adenocarcinoma has a poor clinical prognosis when compared with squamous cell carcinoma. Therefore, the development of new treatment strategies for uterine cervical adenocarcinoma is necessary. Src is a proto-oncogene that is important in cancer progression. Dasatinib is a Src inhibitor that has been reported to be effective when used in combination with anticancer drugs. The present study aimed to confirm Src expression in human cervical adenocarcinoma cell lines and to determine the mechanism underlying the inhibitory effect of dasatinib on Src signaling in vitro. Western blot analysis was performed to investigate Src expression in cervical adenocarcinoma cell lines (HeLa and TCO-2 cells). The cells were cultured for 48 h with the addition of different concentrations of anticancer drugs (paclitaxel or oxaliplatin). Viable cell count was measured using a colorimetric (WST-1) assay. The concentrations of anticancer agents were fixed according to the results obtained, and the same experiments were performed using the drugs in combination with dasatinib at various concentrations to determine the concentrations that significantly affected the number of viable cells. The presence or absence of apoptosis was investigated using a caspase-3/7 assay. Signal transduction in each cell line was examined using western blotting. Src was activated in the two cell lines, and cell proliferation was significantly suppressed by each anticancer drug in combination with 10 μM dasatinib. Caspase-3/7 activity was also increased and Src signaling was suppressed by each anticancer drug in combination with dasatinib. In conclusion, Src is overexpressed in cervical adenocarcinoma cell lines, and dasatinib inhibits intracellular Src signaling and causes apoptosis. The results of the present study suggest that Src may be targeted in novel therapeutic strategies for cervical adenocarcinoma.
• Format (IMT): application/pdf
• Access Restrictions: インターネット公開
• Rights (production): © Takiguchi et al. This is an open access article distributed under the terms of Creative Commons Attribution License (https://creativecommons.org/licenses/by-nc-nd/4.0/).
• Related Material (DOI): 10.3892/etm.2017.5061
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ

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