ID 112973
Title Alternative
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
Author
Takiguchi, Eri Tokushima University
Keywords
Src
dasatinib
paclitaxel
oxaliplatin
cervical adenocarcinoma
Content Type
Thesis or Dissertation
Description
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.
Journal Title
Experimental and Therapeutic Medicine
ISSN
17920981
17921015
NCID
AA12610820
Publisher
Spandidos Publications
Volume
14
Issue
5
Start Page
4293
End Page
4299
Published Date
2017-08-28
Remark
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。
Rights
© 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
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3121号
Diploma Number
甲医第1355号
Granted Date
2018-01-25
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
University Hospital
Medical Sciences