ID 112973
タイトル別表記
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
著者
炬口, 恵理 徳島大学大学院医科学教育部(医学専攻)
キーワード
Src
dasatinib
paclitaxel
oxaliplatin
cervical adenocarcinoma
資料タイプ
学位論文
抄録
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.
掲載誌名
Experimental and Therapeutic Medicine
ISSN
17920981
17921015
cat書誌ID
AA12610820
出版者
Spandidos Publications
14
5
開始ページ
4293
終了ページ
4299
発行日
2017-08-28
備考
内容要旨・審査要旨・論文本文の公開
本論文は,著者Eri Takiguchiの学位論文として提出され,学位審査・授与の対象となっている。
権利情報
© 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/).
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第3121号
学位記番号
甲医第1355号
学位授与年月日
2018-01-25
学位名
博士(医学)
学位授与機関
徳島大学
部局
病院
医学系