| Title |
BH3 Mimetic ABT-199 Enhances the Sensitivity of Gemcitabine in Pancreatic Cancer in vitro and in vivo
|
|---|---|
| Published in |
Digestive Diseases and Sciences, August 2018
|
| DOI | 10.1007/s10620-018-5253-7 |
| Pubmed ID | |
| Authors |
Yi Zhou, Hongchun Liu, Ruyi Xue, Wenqing Tang, Shuncai Zhang |
| Abstract |
Pancreatic cancer is an aggressive malignancy with poor prognosis. Gemcitabine is the standard chemotherapeutic drug used to treat the disease; however, it has a low response rate. Therefore, there is an urgent need to develop new and safe therapies to enhance sensitivity to gemcitabine in treating pancreatic cancer. The synergistic effect of gemcitabine combined with specific B cell CLL/lymphoma 2 (Bcl-2) inhibitor ABT-199 against pancreatic cancer was tested using cell viability, cell cycle, and apoptosis assays in vitro and in an MIA Paca-2 xenograft model in vivo. Its underlying mechanism was explored using western blotting analysis of Bcl-2 family proteins. ABT-199 not only enhanced the effect of gemcitabine on cell growth inhibition but also promoted gemcitabine-induced apoptosis in pancreatic cancer cell lines. Gemcitabine decreased the expression of anti-apoptotic protein Mcl-1 but increased the expression of anti-apoptotic protein Bcl-2. ABT-199 downregulated the gemcitabine-induced production of Bcl-2 and increased the expression of pro-apoptotic protein Bcl-2 interacting protein (BIM). Mouse xenograft experiments also confirmed the synergistic effect of gemcitabine and ABT-199 on tumor growth inhibition and the induction of tumor cell apoptosis. Our results indicated that ABT-199 improved the anti-tumor effect of gemcitabine on pancreatic cancer by downregulating gemcitabine-induced overexpression of Bcl-2. ABT-199 has already been investigated in phase 3 clinical trials for chronic lymphocytic leukemia; therefore, it may serve as a potential drug to improve the sensitivity of pancreatic cancer to gemcitabine. |
X Demographics
The data shown below were collected from the profiles of 5 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 20% |
| Unknown | 4 | 80% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 4 | 80% |
| Science communicators (journalists, bloggers, editors) | 1 | 20% |
Mendeley readers
The data shown below were compiled from readership statistics for 20 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 20 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 5 | 25% |
| Researcher | 3 | 15% |
| Student > Master | 1 | 5% |
| Student > Doctoral Student | 1 | 5% |
| Professor > Associate Professor | 1 | 5% |
| Other | 1 | 5% |
| Unknown | 8 | 40% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 5 | 25% |
| Medicine and Dentistry | 3 | 15% |
| Agricultural and Biological Sciences | 1 | 5% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 5% |
| Immunology and Microbiology | 1 | 5% |
| Other | 1 | 5% |
| Unknown | 8 | 40% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. 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 04 January 2019.
All research outputs
#13,428,001
of 23,854,458 outputs
Outputs from Digestive Diseases and Sciences
#2,442
of 4,304 outputs
Outputs of similar age
#158,884
of 338,012 outputs
Outputs of similar age from Digestive Diseases and Sciences
#23
of 66 outputs
Altmetric has tracked 23,854,458 research outputs across all sources so far. This one is in the 43rd percentile – i.e., 43% of other outputs scored the same or lower than it.
So far Altmetric has tracked 4,304 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.8. This one is in the 43rd percentile – i.e., 43% 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 338,012 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 52% of its contemporaries.
We're also able to compare this research output to 66 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 65% of its contemporaries.