Caro-Maldonado Alfredo, Camacho Laura, Zabala-Letona Amaia, Torrano Verónica, Fernández-Ruiz Sonia, Zamacola-Bascaran Kepa, Arreal Leire, Valcárcel-Jiménez Lorea, Martín-Martín Natalia, Flores Juana M, Cortazar Ana R, Zúñiga-García Patricia, Arruabarrena-Aristorena Amaia, Guillaumond Fabienne, Cabrera Diana, Falcón-Perez Juan M, Aransay Ana M, Gomez-Muñoz Antonio, Olivan Mireia, Morote Juan, Carracedo Arkaitz
CIC bioGUNE, Bizkaia Technology Park, Derio, Spain.
Biochemistry and Molecular Biology Department, University of the Basque Country, Bilbao, Spain.
Oncotarget. 2017 Oct 31;9(2):1494-1504. doi: 10.18632/oncotarget.22217. eCollection 2018 Jan 5.
Prostate cancer is diagnosed late in life, when co-morbidities are frequent. Among them, hypertension, hypercholesterolemia, diabetes or metabolic syndrome exhibit an elevated incidence. In turn, prostate cancer patients frequently undergo chronic pharmacological treatments that could alter disease initiation, progression and therapy response. Here we show that treatment with anti-cholesterolemic drugs, statins, at doses achieved in patients, enhance the pro-tumorigenic activity of obesogenic diets. In addition, the use of a mouse model of prostate cancer and human prostate cancer xenografts revealed that simvastatin administration alone increases prostate cancer aggressiveness. cell line systems supported the notion that this phenomenon occurs, at least in part, through the direct action on cancer cells of low doses of statins, in range of what is observed in human plasma. In sum, our results reveal a prostate cancer experimental system where statins exhibit an undesirable effect, and warrant further research to address the relevance and implications of this observation in human prostate cancer.
前列腺癌通常在患者年老且伴有多种合并症时才被诊断出来。其中,高血压、高胆固醇血症、糖尿病或代谢综合征的发病率较高。反过来,前列腺癌患者经常接受可能会改变疾病发生、发展及治疗反应的长期药物治疗。在此,我们发现,以患者所能达到的剂量使用抗胆固醇药物他汀类药物进行治疗,会增强致肥胖饮食的促肿瘤活性。此外,使用前列腺癌小鼠模型和人前列腺癌异种移植模型发现,单独使用辛伐他汀会增加前列腺癌的侵袭性。细胞系实验支持了这样一种观点,即这种现象至少部分是通过低剂量他汀类药物对癌细胞的直接作用而发生的,这一剂量范围与在人体血浆中观察到的一致。总之,我们的研究结果揭示了一个他汀类药物会产生不良影响的前列腺癌实验系统,有必要进一步研究以探讨这一观察结果在人类前列腺癌中的相关性及意义。