Hankey William, Sunkel Benjamin, Yuan Fuwen, He Haiyan, Thomas-Ahner Jennifer M, Chen Zhong, Clinton Steven K, Huang Jiaoti, Wang Qianben
Department of Pathology, Duke University School of Medicine, Durham, NC 27710, USA; Duke Cancer Institute, Duke University School of Medicine, Durham, NC 27710, USA.
Department of Internal Medicine, The Ohio State University College of Medicine, Columbus, OH 43210, USA.
Transl Oncol. 2020 Sep;13(9):100797. doi: 10.1016/j.tranon.2020.100797. Epub 2020 May 23.
Widespread cGMP-specific phosphodiesterase 5 (PDE5) inhibitor use in male reproductive health and particularly in prostate cancer patients following surgery has generated interest in how these drugs affect the ability of residual tumor cells to proliferate, migrate, and form recurrent colonies. Prostate cancer cell lines were treated with PDE5 inhibitors at clinically relevant concentrations. Proliferation, colony formation, and migration phenotypes remained stable even when cells were co-treated with a stimulator of cGMP synthesis that facilitated cGMP accumulation upon PDE5 inhibition. Surprisingly, supraclinical concentrations of PDE5 inhibitor counteracted proliferation, colony formation, and migration of prostate cancer cell models. These findings provide tumor cell-autonomous evidence in support of the field's predominant view that PDE5 inhibitors are safe adjuvant agents to promote functional recovery of normal tissue after prostatectomy, but do not rule out potential cancer-promoting effects of PDE5 inhibitors in the more complex environment of the prostate.
环磷酸鸟苷特异性磷酸二酯酶5（PDE5）抑制剂在男性生殖健康领域广泛应用，尤其是在前列腺癌患者术后，这引发了人们对这些药物如何影响残留肿瘤细胞增殖、迁移和形成复发菌落能力的兴趣。用临床相关浓度的PDE5抑制剂处理前列腺癌细胞系。即使细胞与促进环磷酸鸟苷合成的刺激剂共同处理，在PDE5抑制时促进环磷酸鸟苷积累，增殖、菌落形成和迁移表型仍保持稳定。令人惊讶的是，超临床浓度的PDE5抑制剂可抵消前列腺癌细胞模型的增殖、菌落形成和迁移。这些发现提供了肿瘤细胞自主性证据，支持该领域的主流观点，即PDE5抑制剂是促进前列腺切除术后正常组织功能恢复的安全辅助药物，但不排除PDE5抑制剂在更复杂的前列腺环境中具有潜在促癌作用。
