Simvastatin delays CRPC metastasis and AR antagonist resistance by regulating the expression of caveolin‑1.

[pjoshea13]

New cell study below [1].

"Cav‑1 [caveolin‑1] was overexpressed in CRPC. Furthermore, ... Cav‑1 expression in tumors was an independent risk factor for the occurrence of CRPC and was associated with a shorter recurrence‑free survival time in patients with CRPC."

"Importantly, simvastatin was able to augment the anticancer effects of androgen receptor antagonists by downregulating the expression of Cav‑1."

"Collectively, the findings of this study provide evidence that Cav‑1 is a promising predictive biomarker for CRPC and that lowering cholesterol levels with simvastatin or interfering with the expression of Cav‑1 may prove to be a useful strategy with which to prevent and/or treat CRPC."

-Patrick

[1] Int J Oncol. 2019 Jun;54(6):2054-2068. doi: 10.3892/ijo.2019.4774. Epub 2019 Apr 5.

Simvastatin delays castration‑resistant prostate cancer metastasis and androgen receptor antagonist resistance by regulating the expression of caveolin‑1.

Gao Y1, Li L1, Li T1, Ma L2, Yuan M3, Sun W3, Cheng HL3, Niu L1, Du Z3, Quan Z3, Fan Y1, Fan J1, Luo C1, Wu X3.

Author information

1

Department of Laboratory Diagnosis, Chongqing Medical University, Chongqing 408000, P.R. China.

2

Department of Laboratory Diagnosis, The First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang 154000, P.R. China.

3

Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 408000, P.R. China.

Abstract

The failure of androgen deprivation therapy in prostate cancer treatment mainly results from drug resistance to androgen receptor antagonists. Although an aberrant caveolin‑1 (Cav‑1) expression has been reported in multiple tumor cell lines, it is unknown whether it is responsible for the progression of castration‑resistant prostate cancer (CRPC). Thus, the aim of the present study was to determine whether Cav‑1 can be used as a key molecule for the prevention and treatment of CRPC, and to explore its mechanism of action in CRPC. For this purpose, tissue and serum samples from patients with primary prostate cancer and CRPC were analyzed using immunohistochemistry and enzyme‑linked immunosorbent assay, which revealed that Cav‑1 was overexpressed in CRPC. Furthermore, Kaplan‑Meier survival analysis and univariate Cox proportional hazards regression analysis demonstrated that Cav‑1 expression in tumors was an independent risk factor for the occurrence of CRPC and was associated with a shorter recurrence‑free survival time in patients with CRPC. Receiver operating characteristic curves suggested that serum Cav‑1 could be used as a diagnostic biomarker for CRPC (area under the curve, 0.876) using a cut‑off value of 0.68 ng/ml (with a sensitivity of 82.1% and specificity of 80%). In addition, it was determined that Cav‑1 induced the invasion and migration of CRPC cells by the activation of the H‑Ras/phosphoinositide‑specific phospholipase Cε signaling cascade in the cell membrane caveolae. Importantly, simvastatin was able to augment the anticancer effects of androgen receptor antagonists by downregulating the expression of Cav‑1. Collectively, the findings of this study provide evidence that Cav‑1 is a promising predictive biomarker for CRPC and that lowering cholesterol levels with simvastatin or interfering with the expression of Cav‑1 may prove to be a useful strategy with which to prevent and/or treat CRPC.

PMID: 31081050 DOI: 10.3892/ijo.2019.4774

[jdm3]

Yay! Thanks.

I'm up to simvastatin, coffee, wine, dark chocolate, vitamin D3, and broccoli sprouts. Life is good.

[Ralph1966]

Thanks Patrick,

What is the minimum daily dosage to use?

Is it only simvastatin that works or we can use other types of statins?

Ralph

[pjoshea13 in reply to Ralph1966]

Researchers seem to prefer Simvastatin - presumably because prior studies have used it. LOL. I have used Simvastatin for many years & that's my excuse.

It may not be the best, but there are conflicting results in studies that have considered multiple statins.

Studies seem to agree that the benefit is dose-related. The max dose of Simvastatin in the U.S. is 40 mg, but 80 mg is available elsewhere. I might consider another statin if the maximum dose had a higher Simvastatin-eguivalency than 40 mg.

-Patrick