| Title |
Geldanamycin, an inhibitor of Hsp90, increases paclitaxel-mediated toxicity in ovarian cancer cells through sustained activation of the p38/H2AX axis
|
|---|---|
| Published in |
Tumor Biology, September 2016
|
| DOI | 10.1007/s13277-016-5297-2 |
| Pubmed ID | |
| Authors |
Qingqing Mo, Yu Zhang, Xin Jin, Yue Gao, Yuan Wu, Xing Hao, Qinglei Gao, Pingbo Chen |
| Abstract |
Paclitaxel is a mitotic inhibitor used in ovarian cancer chemotherapy. Unfortunately, due to the rapid genetic and epigenetic changes in adaptation to stress induced by anticancer drugs, cancer cells are often able to become resistant to single or multiple anticancer agents. However, it remains largely unknown how paclitaxel resistance happens. In this study, we generated a cell line of acquired resistance to paclitaxel therapy, A2780T, which is cross-resistant to other antimitotic drugs, such as PLK1 inhibitor or AURKA inhibitor. Immunoblotting revealed significant alterations in cell-cycle-related and apoptotic-related proteins involved in key signaling pathways. In particular, phosphorylation of p38, which activates H2AX, was significantly decreased in A2780T cells compared to the parental A2780 cells. Geldanamycin (GA), an inhibitor of Hsp90, sustained activation of the p38/H2AX axis, and A2780T cells were shown to be more sensitive to GA compared to A2780 cells. Furthermore, treatment of A2780 and A2780T cells with GA significantly enhanced sensitivity to paclitaxel. Meanwhile, GA cooperated with paclitaxel to suppress tumor growth in a mouse ovarian cancer xenograft model. In conclusion, GA may sensitize a subset of ovarian cancer to paclitaxel, particularly those tumors in which resistance is driven by inactivation of p38/H2AX axis. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| France | 1 | 50% |
| Unknown | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 21 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 21 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 4 | 19% |
| Student > Master | 3 | 14% |
| Student > Bachelor | 2 | 10% |
| Lecturer | 1 | 5% |
| Student > Doctoral Student | 1 | 5% |
| Other | 2 | 10% |
| Unknown | 8 | 38% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 4 | 19% |
| Medicine and Dentistry | 3 | 14% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 5% |
| Mathematics | 1 | 5% |
| Social Sciences | 1 | 5% |
| Other | 3 | 14% |
| Unknown | 8 | 38% |
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 09 February 2017.
All research outputs
#18,471,305
of 22,888,307 outputs
Outputs from Tumor Biology
#1,370
of 2,623 outputs
Outputs of similar age
#243,646
of 321,166 outputs
Outputs of similar age from Tumor Biology
#47
of 94 outputs
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