Advanced Prostate Cancer

Simvastatin & Docetaxel?

New cell study below.

Bottom line: Simvastatin might enhance Taxotere killing potential.

-Patrick

ncbi.nlm.nih.gov/pubmed/288...

BMB Rep. 2017 Aug 11. pii: 3861. [Epub ahead of print]

Identification of simvastatin-regulated targets associated with JNK activation in DU145 human prostate cancer cell death signaling.

Jung EJ, Chung KH, Kim CW1.

Author information

Abstract

In this study, our results showed that the c-Jun N-terminal kinase (JNK) activation was associated with the enhancement of docetaxel-induced cytotoxicity by simvastatin in DU145 human prostate cancer cells. To better understand the basic molecular mechanisms, we investigated simvastatin-regulated targets during simvastatin-induced cell death in DU145 cells using two-dimensional (2D) proteomic analysis. Thus, vimentin, Ras-related protein Rab-1B (RAB1B), cytoplasmic hydroxymethylglutaryl-CoA synthase (cHMGCS), thioredoxin domain-containing protein 5 (TXNDC5), heterogeneous nuclear ribonucleoprotein K (hnRNP K), N-myc downstream-regulated gene 1 (NDRG1) and isopentenyl-diphosphate Delta-isomerase 1 (IDI1) protein spots were identified as simvastatin-regulated targets involved in DU145 cell death signaling pathways. Moreover, the upregulation of NDRG1 and IDI protein levels by combination treatment of docetaxel and simvastatin was significantly inhibited by the JNK inhibitor SP600125. These results suggest that, at least, NDRG1 and IDI could play an important role in DU145 cell death signaling as simvastatin-regulated targets associated with JNK activation.

PMID: 28803608

3 Replies
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I wonder if other statins would have a similar benefit. Simvastatin severely aggravates my GERD / Reflux. I had to switch to atorvastatin.

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In general, it is the lipophilic statins that show benefit in PCa:

"Atorvastatin, lovastatin, and simvastatin are lipophilic, whereas pravastatin, rosuvastatin, and fluvastatin are more hydrophilic." [MedScape]

Whether Atorvastatin (or Lovastatin) would perform as well as Simvastatin in the Docetaxel study, I can't say. But the authors make no special claim for Simvastatin in the Abstract.

-Patrick

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Lipophilic statins such as Simvastatin may also increase the duration for Zytiga. Recent research study from Dana Farber and John Hopkins.

Rich

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