Discoidin domain receptor 1a (DDR1a) confers 5-fluorouracil cytotoxicity in LoVo cell via PI3K/AKT/Bcl-2 pathway

5-Fluorouracil (5-FU) is a common chemotherapy drug for patients with advanced colorectal cancer; however, many patients develop resistance to 5-FU and suffer from treatment failure. Discoidin domain receptor 1 (DDR1) is upregulated in multiple cancers and positively associated with chemoresistance....

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Main Authors: Chen, H.-L (Author), Han, T.-Y (Author), Jin, Z.-X (Author), Li, Y. (Author), Song, F.-X (Author), Wang, X.-J (Author), Xiong, B. (Author), Zhang, D.-K (Author)
Format: Article
Language:English
Published: Taylor and Francis Ltd. 2022
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Online Access:View Fulltext in Publisher
LEADER 02171nam a2200289Ia 4500
001 10-1080-21655979-2022-2060782
008 220425s2022 CNT 000 0 und d
020 |a 21655979 (ISSN) 
245 1 0 |a Discoidin domain receptor 1a (DDR1a) confers 5-fluorouracil cytotoxicity in LoVo cell via PI3K/AKT/Bcl-2 pathway 
260 0 |b Taylor and Francis Ltd.  |c 2022 
300 |a 10 
856 |z View Fulltext in Publisher  |u https://doi.org/10.1080/21655979.2022.2060782 
520 3 |a 5-Fluorouracil (5-FU) is a common chemotherapy drug for patients with advanced colorectal cancer; however, many patients develop resistance to 5-FU and suffer from treatment failure. Discoidin domain receptor 1 (DDR1) is upregulated in multiple cancers and positively associated with chemoresistance. We explored the effect of DDR1a on the cytotoxicity induced by 5-FU in LoVo cells and the underlying mechanism. Therefore, DDR1a overexpression (DDR1ahigh) and knockdown in LoVo cell lines (shDDR1a) were constructed to detect cell viability and cytotoxicity induced by 5-FU. The results showed that cell viability of DDR1ahigh cells was higher in comparison with that of the control group. When 5-FU (5 µM) was administered, the percentage of apoptotic cells, cytochrome C release and caspase-3 activity was found to be higher in the shDDR1a group than that in the control group. Both of PI3K and MDM2 proteins level decreased in DDR1ahigh and shDDR1a, but the BAX/Bcl-2 level in the shDDR1a group increased compared to that in the control. Therefore, DDR1a might be a potential therapeutic target for 5-FU chemoresistance in colorectal cancer. © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. 
650 0 4 |a 5-fluorouracil 
650 0 4 |a colorectal cancer 
650 0 4 |a cytotoxicity 
650 0 4 |a Discoidin domain receptor 1a 
650 0 4 |a proliferation 
700 1 |a Chen, H.-L.  |e author 
700 1 |a Han, T.-Y.  |e author 
700 1 |a Jin, Z.-X.  |e author 
700 1 |a Li, Y.  |e author 
700 1 |a Song, F.-X.  |e author 
700 1 |a Wang, X.-J.  |e author 
700 1 |a Xiong, B.  |e author 
700 1 |a Zhang, D.-K.  |e author 
773 |t Bioengineered