Patrick O'Shea and others interesting in the effects of statins on prostate cancer suppression, do you find anything about this study that reinforces the use of Simvastatin over other statins, or is it insignificant because it's not a study on men?
I didn't try to translate the amount/dosage in this study, and how it would compare to a man, so I can't tell if it's relevant in that regard or not.
After switching from Crestor to Pitivastain, and then recently to Simvastain, I've had general muscle and joint aching, which is really irritating and demoralizing. I wish the industry would do some tests on combining more than one statin, in order to get a wider defense against different types of PCa cells. I'm thinking about going back to Crestor, but with a low dose of 5mg, combined with 5 or 10mg of Zetia. I did the research this week, and it looks like a good option for those who are getting muscle and joint aches.
Here is the study that I referenced above: mdpi.com/2227-9059/11/1/29
and here is an clip from that study report:
"Simvastatin demonstrated the strongest growth inhibitory effect of all three statins, followed by atorvastatin and rosuvastatin, which in fact did not express any significant inhibition on the investigated cell lines (Figure 1A). At a concentration of 1 µM, simvastatin accomplished a >50% reduction of cell growth representing the IC50, whereas atorvastatin reached the IC50 mark at a concentration of 3 µM in the same cell lines. Responsiveness to the three statins also strongly differed among the cell lines. Simvastatin and atorvastatin had the strongest growth-inhibitory effect in androgen-insensitive PC-3 cells, followed by LNCaP cells, which mimic hormone-sensitive PCa. The two castration-resistant cell lines, LNCaPabl and 22Rv1, on the other hand, were clearly less sensitive to statin treatment. Representative images of each cell line after treatment with the most effective dose of 5 µM are shown in Figure 1B.
Corresponding with the effect obtained on cell viability, simvastatin significantly induced apoptosis in LNCaP and PC-3 cells and to a much lesser extend in LNCaPabl and 22Rv1 cells (Figure 1C). Atorvastatin, by contrast, only induced apoptosis in PC-3 cells whereas rosuvastatin did not induce apoptosis in any of the cell lines (Figure 1A,B).
In combination with 5 µM of the anti-androgen enzalutamide, there was a weak increase in growth inhibition of androgen-sensitive LNCaP cells compared to statins alone, particularly at lower concentrations between 2 and 4 µM (Figure 1A), whereas there was no apparent additive effect of statins and enzalutamide in PC-3 cells. In castration-resistant LNCaPabl cells, enzalutamide combined with atorvastatin resulted in the most prominent growth inhibition. Notably, simvastatin and also rosuvastatin were able to increase the effect of enzalutamide in 22Rv1 cells. These data suggest that statins may in fact be able to enhance the tumor growth inhibitory effect of enzalutamide, however, depending on the type of statin and the tumor cell line.
3.2. Differential Effects of Statins on the Expression of HMGCR
One of the possible explanations for the differential effects of statins observed in PCa cells is the transcriptional upregulation of enzymes of the mevalonate pathway by sterol regulatory element binding protein 2 (SREBP2), a feedback mechanism that is activated by statin treatment. Previous studies have demonstrated that AR-negative PC-3 cells lack SREBP2 expression and are therefore highly responsive to statins [26]. Therefore, we next investigated changes in HMGCR expression after treatment of our 4 PCa cell lines with the three different statins through qPCR. As depicted in Figure 2A, simvastatin treatment induced an upregulation of HMGCR in AR-positive LNCaP, LNCaPabl and 22Rv1 cells but not in AR-negative PC-3 cells, confirming previously published results [26]. Similarly, HMGCS1 was significantly upregulated by simvastatin in LNCaP, LNCaPabl and 22Rv1 cells but did not affect the expression in PC-3 cells (Figure 2B). Treatment with atorvastatin and rosuvastatin, by contrast, increased the expression of HMGCR and HMGCS1 in all 4 cell lines, including PC-3 cells, indicating that a lack of response to the different statins cannot solely be explained by the SREBP2 mediated feedback mechanism.
3.3. Long-Term Effects of Simvastatin
Since simvastatin exhibited the strongest anti-proliferative effect on PCa cells in our short-term experiments, we used this statin to study the effects of long-term treatment on PCa cell growth. For that reason, LNCaP, LNCaPabl and PC-3 cells were cultivated in a medium containing simvastatin over a period of 6 months."
