Abstract：
BACKGROUND:Hepatocellular carcinoma (HCC) is one of the most common types of malignant tumour and has poor prognosis. Currently, systematic chemotherapy is the only approach to prolong survival. Thus the development of new treatment regimens is urgently needed to improve the therapeutic efficacy. Our study intended to assess the combination of dasatinib and irinotecan against HCC and made an effort to develop a potential medical choice for advanced HCC patients. METHODS:We used SRB colorimetric assay and clonogenic assay to assess antitumour effect in vitro and HCC xenograft model to assess antitumour effect in vivo. We applied flow cytometry and western blotting to explore the mechanism of the combined therapy. Knockdown and overexpression of PLK1 are also applied for validation. RESULTS:We confirmed that dasatinib has synergistic effect with irinotecan (or SN38) on HCC both in vitro and in vivo. The effect is due to arisen apoptosis rate of HCC cells that is accompanied by mitochondria dysfunction. The enhanced antitumour efficacy of SN38 could be explained by additional inhibition of PLK1, which is triggered by dasatinib. Unlike existed PLK1 inhibitors, dasatinib does not inhibit PLK1 activity in a direct way. Instead, we found that dasatinib reduces PLK1 level by interfering with its protein synthesis progress. We validated that this kind of downregulation of PLK1 level has a key role in the synergistic effect of the two agents. CONCLUSIONS:Dasatinib is able to reinforce the anti-HCC efficacy of irinotecan/SN38 by downregulation of PLK1 synthesis. The combination of the two agents might be a potential medical choice for HCC therapy.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Xu L,Zhu Y,Shao J,Chen M,Yan H,Li G,Zhu Y,Xu Z,Yang B,Luo P,He Qdoi
10.1038/bjc.2017.55subject
Has Abstractpub_date
2017-04-11 00:00:00pages
1027-1036issue
8eissn
0007-0920issn
1532-1827pii
bjc201755journal_volume
116pub_type
杂志文章abstract：BACKGROUND:Magnetic resonance imaging (MRI) has been proposed to guide breast cancer surgery by measuring residual tumour after neoadjuvant chemotherapy. This study-level meta-analysis examines MRI's agreement with pathology, compares MRI with alternative tests and investigates consistency between different measures of...
journal_title：British journal of cancer
pub_type： 杂志文章,meta分析,评审
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更新日期：2013-09-17 00:00:00
abstract：BACKGROUND:Earlier studies have shown raised risks of leukaemia and non-Hodgkin lymphoma in children, teenagers and young adults resident either at birth or diagnosis in Seascale. Some increases in cancer risk in these age groups have also been noted among those living around Dounreay. We aimed to update previous analy...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2014.357
更新日期：2014-10-28 00:00:00
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pub_type： 杂志文章
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journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1995.382
更新日期：1995-09-01 00:00:00
abstract：:Members of the public are increasingly consulted over health care and research priorities. Patient involvement in determining cancer research priorities, however, has remained underdeveloped. This paper presents the findings of the first consultation to be conducted with UK cancer patients concerning research prioriti...
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doi：10.1038/sj.bjc.6603662
更新日期：2007-03-26 00:00:00
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journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1998.129
更新日期：1998-03-01 00:00:00
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journal_title：British journal of cancer
pub_type： 杂志文章
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更新日期：1994-08-01 00:00:00
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pub_type： 杂志文章
doi：10.1038/sj.bjc.6601766
更新日期：2004-05-04 00:00:00
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pub_type： 杂志文章
doi：10.1038/s41416-018-0323-3
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doi：10.1038/sj.bjc.6605097
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journal_title：British journal of cancer
pub_type： 临床试验,杂志文章
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更新日期：1996-04-01 00:00:00
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journal_title：British journal of cancer
pub_type： 杂志文章,随机对照试验
doi：10.1038/bjc.2012.100
更新日期：2012-04-24 00:00:00
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pub_type： 杂志文章
doi：10.1038/bjc.1995.193
更新日期：1995-05-01 00:00:00
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journal_title：British journal of cancer
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doi：10.1038/bjc.1990.56
更新日期：1990-02-01 00:00:00
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pub_type： 杂志文章
doi：10.1038/sj.bjc.6604048
更新日期：2007-11-19 00:00:00
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pub_type： 杂志文章
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pub_type： 杂志文章
doi：10.1038/bjc.1991.387
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pub_type： 临床试验,杂志文章
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doi：10.1038/sj.bjc.6601124
更新日期：2003-08-04 00:00:00
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更新日期：2007-06-18 00:00:00
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journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1983.60
更新日期：1983-03-01 00:00:00
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journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1986.224
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更新日期：1978-08-01 00:00:00
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pub_type： 杂志文章
doi：10.1038/bjc.1993.17
更新日期：1993-01-01 00:00:00
abstract：:The relationship between skin tumours in man and exposure to polyaromatic hydrocarbons has been studied in lathe operators exposed to cutting oils. Seven cases of scrotal cancer and 13 cases of senile keratosis and keratoacanthoma were observed. The risk varied as the 1.6th power of duration of exposure for cancer on ...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1990.435
更新日期：1990-12-01 00:00:00
