Reference - Detail
| RRC ID | 51699 |
|---|---|
| Author | Ogura T, Tanaka Y, Tamaki H, Harada M. |
| Title | Docetaxel induces Bcl-2- and pro-apoptotic caspase-independent death of human prostate cancer DU145 cells. |
| Journal | Int J Oncol |
| Abstract |
Docetaxel is a useful chemotherapeutic agent for the first-line treatment of hormone-refractory prostate cancer. Abnormal expression of Bcl-2 is commonly found in cancer cells, which increases their anti-apoptotic potency and chemoresistance. We investigated the effects of Bcl-2 expression status on the susceptibility of DU145 cells, an androgen-independent human prostate cancer cell line, to docetaxel and other anticancer agents. A panel of Bcl-2-expressing DU145 cell lines was established. Bcl-2 expression levels were unrelated to the susceptibility of DU145 cells to docetaxel. The sensitivity of DU145 cells to cisplatin fluctuated, and the sensitivity to tumor necrosis factor (TNF)-α was decreased by Bcl-2 overexpression. In a xenograft mouse model, overexpression of Bcl-2 drastically decreased the sensitivity of DU145 cells to cisplatin and TNF-α; however, there was no change in the response to docetaxel. Fluorescent microscopy revealed that Bcl-2-overexpression had no effect on the docetaxel-induced death of DU145 cells, but significantly decreased DU145 cell death induced by cisplatin or TNF-α. Interestingly, docetaxel hardly induced caspase-3/7 activation in control or Bcl-2-overexpressing DU145 cells, but did at a low level in LNCaP cells, another prostate cancer cell line. Moreover, in contrast to LNCaP cells, the reduced viabilities of docetaxel-treated control and Bcl-2-overexpressing DU145 cells were not restored by the addition of either a Bid inhibitor or a panel of pro-apoptotic caspase inhibitors. These findings indicate that the antitumor effects of docetaxel on DU145 cells are independent of both Bcl-2 and pro-apoptotic caspases. |
| Volume | 48(6) |
| Pages | 2330-8 |
| Published | 2016-6-1 |
| DOI | 10.3892/ijo.2016.3482 |
| PMID | 27082738 |
| PMC | PMC4864052 |
| MeSH | Animals Antineoplastic Agents / pharmacology* Apoptosis / drug effects Apoptosis / physiology Caspases / biosynthesis* Cell Line, Tumor Docetaxel Drug Screening Assays, Antitumor Humans Male Mice Mice, Inbred C3H Mice, Nude Prostatic Neoplasms / drug therapy* Prostatic Neoplasms / genetics Prostatic Neoplasms / metabolism Prostatic Neoplasms / pathology Proto-Oncogene Proteins c-bcl-2 / biosynthesis* Proto-Oncogene Proteins c-bcl-2 / genetics Taxoids / pharmacology* Transfection Xenograft Model Antitumor Assays |
| IF | 3.899 |
| Times Cited | 16 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | LNCap.FGC(RCB2144) |