Department of Morphology, Institute of Biosciences, Sao Paulo State University (UNESP), Rua Professor Doutor Antonio Celso Wagner Zanin, 250, Botucatu, SP, 18618-689, Brazil.
Institute of Biosciences, Humanities and Exact Sciences, Sao Paulo State University (UNESP), São José do Rio Preto, SP, Brazil.
Horm Cancer. 2018 Jun;9(3):175-187. doi: 10.1007/s12672-018-0323-z. Epub 2018 Jan 23.
Use of drug combinations that target different pathways involved in the development and progression of prostate cancer (PCa) has emerged as an alternative to overcome the resistance caused by drug monotherapies. The antiandrogen abiraterone acetate and the PI3K/Akt inhibitor NVP-BEZ235 (BEZ235) may be suitable options for the prevention of drug resistance and the inhibition of PCa progression. The aim of the present study was to evaluate whether abiraterone acetate and BEZ235 achieve superior therapeutic effects to either drug administered as monotherapy, in the early stages of PCa in an androgen-dependent system. Our study showed that each drug might impair tumor growth by reducing proliferation and increasing cell death when administered as monotherapy. However, tumor growth continued to progress with each drug monotherapy and some important side effects were related to BEZ. Conversely, when used in combination, the drugs impaired the inflammatory response, decreased hyperplastic lesions, and blocked tumor progression from premalignant to a malignant stage. Our data showed that the strategy to block the androgenic and PI3K/AKT/mTOR pathway is an effective therapeutic option and should be investigated including distinct PI3K pathway inhibitors.
使用针对前列腺癌（PCa）发展和进展中涉及的不同途径的药物组合已成为克服药物单药治疗引起的耐药性的一种替代方法。抗雄激素醋酸阿比特龙和 PI3K/Akt 抑制剂 NVP-BEZ235（BEZ235）可能是预防耐药性和抑制 PCa 进展的合适选择。本研究旨在评估在雄激素依赖性系统中，PCa 的早期阶段，醋酸阿比特龙和 BEZ235 是否比单药治疗具有更好的治疗效果。我们的研究表明，每种药物单用时可能通过减少增殖和增加细胞死亡来抑制肿瘤生长。然而，随着每种药物的单药治疗，肿瘤生长仍在继续进展，并且与 BEZ 相关的一些重要副作用。相反，当联合使用时，这些药物会抑制炎症反应，减少增生性病变，并阻止肿瘤从癌前阶段向恶性阶段进展。我们的数据表明，阻断雄激素和 PI3K/AKT/mTOR 通路的策略是一种有效的治疗选择，应该进行研究，包括不同的 PI3K 通路抑制剂。
