The combination of poly(ADP-ribose) polymerase inhibitor and statin inhibits the proliferation of human castration-resistant and taxane-resistant prostate cancer cells in vitro and in vivo

Sep 23, 2026

Simvastatin is examined as a sensitizer for castration-resistant prostate cancer when combined with the PARP inhibitor olaparib. The study evaluates how simvastatin modulates DNA repair gene expression, including BRCA1/BRCA2 and other repair factors, and whether this enhances olaparib cytocidal effects. Experiments use prostate cancer cell lines and androgen-independent models, plus in vivo xenografts, to measure proliferation inhibition and treatment synergy.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages11

Reading Time28 min

AccessFree to download

Abstract

Background

Methods

Results

Conclusions

Background

Androgen deprivation and CRPC therapies

Statins in prostate cancer

Olaparib and PARP inhibition

Sekine et al. BMC Cancer (2025) 25:521 BMC Cancer [https://doi.org/10.1186/s12885-025-13895-6](https://doi.org/10.1186/s12885-025-13895-6) RESEARCH Open Access The combination of poly(ADP-ribose) polymerase inhibitor and statin inhibits the proliferation of human castration-resistant and taxane-resistant prostate cancer cells in vitro and in vivo Yoshitaka Sekine 1*, Daisuke Oka 1, Akira Ohtsu 1, Hiroshi Nakayama 1, Takeshi Miyao 1, Yoshiyuki Miyazawa 1, Seiji Arai 1, Hidekazu Koike 1, Hiroshi Matsui 1, Yasuhiro Shibata 1 and Kazuhiro Suzuki 1 Abstract Background Olaparib exhibits antitumor effects in castration-resistant prostate cancer patients with germline mutations in DNA repair genes. We previously reported that simvastatin reduced the expression of DNA repair genes in PC-3 cells. The efficacy of combination therapy using olaparib and simvastatin as“BRCAness” in castration-resistant and taxane-resistant prostate cancers was evaluated in this study. Methods PC-3, LNCaP, and 22Rv1 human prostate cancer cell lines were used to develop androgen-independent LNCaP cells (LNCaP-LA) . mRNA and protein expression levels were evaluated by quantitative real-time polymerase chain reaction and western blot analysis, respectively. Cell viability was determined using the MTS assay and cell counts. All evaluations were performed on cells treated with simvastatin with or without olaparib. Results The mRNA levels of BRCA1, BRCA2, RAD51, FANCD2, FANCG, FANCA, BARD1, RFC3, RFC4, and RFC5, which are known DNA repair genes, were downregulated by simvastatin in androgen-independent prostate cancer cells, such as PC-3, LNCaP-LA, and 22Rv1 cells. In contrast, the expression of all these genes remained unchanged in androgendependent LNCaP cells following treatment with simvastatin. Furthermore, simvastatin increased the expression of above stated genes in normal prostate stromal cells (PrSC) . The reduction in BRCA1 and BRCA2 expression following siRNA transfection increased the cytocidal effects of Olaparib in PC-3 and LNCaP-LA cells. The combination of olapariband simvastatin further inhibited cell proliferation compared to monotherapy with either drug in PC-3, 22Rv1, and LNCaP-LA cells but not in PrSC cells. In a 22Rv1-derived mouse xenograft model, the combination of olaparib and simvastatin enhanced the inhibition of cell proliferation. Moreover, we established a 22Rv1 cell line with acquired resistance to Cabazitaxel (22Rv1-CR) . In 22Rv1-CR cells, simvastatin also decreased the expression of BRCA1, BRCA2, *Correspondence: Yoshitaka Sekine [ysekine@gunma-u.ac.jp](ysekine@gunma-u.ac.jp) Full list of author information is available at the end of the article © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creati](http://creati)[vecommons.org/l](vecommons.org/l)icenses/by-nc-nd/4.0/. Sekine et al. BMC Cancer (2025) 25:521 Page 2 of 11 and FANCA, and the combination of olaparib and simvastatin further enhanced the inhibition of cell proliferation compared with treatment with either of

FAQs

What therapeutic combination is evaluated in this study?

The study evaluates combining the poly(ADP-ribose) polymerase inhibitor olaparib with the statin simvastatin to affect castration-resistant and taxane-resistant prostate cancer cells.

How does simvastatin influence DNA repair genes in the experiments?

Simvastatin downregulates multiple DNA repair genes, including BRCA1 and BRCA2, in androgen-independent prostate cancer cell models.

Does the combination therapy outperform single-agent treatment?

In castration-resistant/taxane-resistant cell models, the combination more strongly inhibits cell proliferation than either drug alone, while effects are not observed in normal prostate stromal cells.

Sep 23, 2026

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