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EHD1 confers resistance to cisplatin in non-small cell lung cancer by regulating intracellular cisplatin concentrations

Overview of attention for article published in BMC Cancer, July 2016
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Title
EHD1 confers resistance to cisplatin in non-small cell lung cancer by regulating intracellular cisplatin concentrations
Published in
BMC Cancer, July 2016
DOI 10.1186/s12885-016-2527-3
Pubmed ID
Authors

Jing Gao, Qingwei Meng, Yanbin Zhao, Xuesong Chen, Li Cai

Abstract

Non-small cell lung cancer (NSCLC) is one of the most aggressive types of cancer. However, resistance to cisplatin (CDDP) remains a major challenge in NSCLC treatment. The purpose of this study was to investigate the ability of EHD1 [Eps15 homology (EH) domain - containing protein 1] to confer CDDP resistance in NSCLC cells and to investigate mechanisms of this resistance. The associations between EHD1 expression in NSCLC specimens and clinicopathological features, including prognosis, were assessed by immunohistochemistry (IHC). Using DNA microarrays, we performed a genome-wide analysis of cisplatin-resistant NSCLC cells to identify the involvement of the EHD1 gene in this resistance. We overexpressed and knocked down EHD1 in cell lines to investigate the effect of this gene on proliferation and apoptosis. A quantitative analytical method for assessing CDDP in cells was developed. High-performance liquid chromatography was used to measure the concentration of cisplatin in cells. The immunohistochemistry assay showed that adjuvant chemotherapy-treated NSCLC patients expressing EHD1 exhibited reduced OS compared with patients who did not express EHD1 (P = 0.01). Moreover, DNA microarrays indicated that the EHD1 gene was upregulated in CDDP- resistant NSCLC cells. The IC50 value of CDDP in cells that overexpressed EHD1 was 3.3-fold greater than that in the A549-control line, and the IC50 value of EHD1 knockdown cells was at least 5.2-fold lower than that of the control cells, as evidenced by a CCK-8 assay. We found that the percentage of early apoptotic cells was significantly decreased in A549-EHD1 cells, but the rates of early apoptosis were higher in the EHD1 knockdown cell line than in the A549/DDP control line, as indicated by a flow cytometry analysis. High-performance liquid chromatography (HPLC) showed that the total platinum level was lower in A549-EHD1 cells than in control cells, and the concentration of CDDP was higher in the EHD1 knockdown cells than in the A549/DDP control cells. We conclude that EHD1 is required for tumour growth and that it is a regulator of CDDP accumulation and cytotoxicity. The selective knockdown of EHD1 in tumours offers a strategy for enhancing the efficacy of CDDP.

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 22 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 22 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 7 32%
Student > Ph. D. Student 3 14%
Student > Master 2 9%
Student > Postgraduate 2 9%
Researcher 1 5%
Other 1 5%
Unknown 6 27%
Readers by discipline Count As %
Pharmacology, Toxicology and Pharmaceutical Science 4 18%
Biochemistry, Genetics and Molecular Biology 3 14%
Agricultural and Biological Sciences 3 14%
Medicine and Dentistry 2 9%
Earth and Planetary Sciences 1 5%
Other 1 5%
Unknown 8 36%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 19 July 2016.
All research outputs
#20,336,031
of 22,881,154 outputs
Outputs from BMC Cancer
#6,506
of 8,325 outputs
Outputs of similar age
#308,685
of 354,668 outputs
Outputs of similar age from BMC Cancer
#185
of 262 outputs
Altmetric has tracked 22,881,154 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 8,325 research outputs from this source. They receive a mean Attention Score of 4.3. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 354,668 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 262 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.