Hashemi Mehrdad, Taheriazam Afshin, Daneii Pouria, Hassanpour Aria, Kakavand Amirabbas, Rezaei Shamin, Hejazi Elahe Sadat, Aboutalebi Maryam, Gholamrezaie Hamidreza, Saebfar Hamidreza, Salimimoghadam Shokooh, Mirzaei Sepideh, Entezari Maliheh, Samarghandian Saeed
Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
J Cell Commun Signal. 2023 Sep;17(3):423-443. doi: 10.1007/s12079-022-00702-1. Epub 2022 Nov 11.
Urological cancers have obtained much attention in recent years due to their mortality and morbidity. The most common and malignant tumor of urological cancers is prostate cancer that imposes high socioeconomic costs on public life and androgen-deprivation therapy, surgery, and combination of chemotherapy and radiotherapy are employed in its treatment. PI3K/Akt signaling is an oncogenic pathway responsible for migration, proliferation and drug resistance in various cancers. In the present review, the role of PI3K/Akt signaling in prostate cancer progression is highlighted. The activation of PI3K/Akt signaling occurs in prostate cancer, while PTEN as inhibitor of PI3K/Akt shows down-regulation. Stimulation of PI3K/Akt signaling promotes survival of prostate tumor cells and prevents apoptosis. The cell cycle progression and proliferation rate of prostate tumor cells increase by PI3K/Akt signaling induction. PI3K/Akt signaling stimulates EMT and enhances metastasis of prostate tumor cells. Silencing PI3K/Akt signaling impairs growth and metastasis of prostate tumor cells. Activation of PI3K/Akt signaling mediates drug resistance and reduces radio-sensitivity of prostate tumor cells. Anti-tumor compounds suppress PI3K/Akt signaling in impairing prostate tumor progression. Furthermore, upstream regulators such as miRNAs, lncRNAs and circRNAs regulate PI3K/Akt signaling and it has clinical implications for prostate cancer patients.
近年来，泌尿系统癌症因其死亡率和发病率受到了广泛关注。泌尿系统癌症中最常见且恶性程度最高的肿瘤是前列腺癌，它给公众生活带来了高昂的社会经济成本，其治疗方法包括雄激素剥夺疗法、手术以及化疗与放疗的联合应用。PI3K/Akt信号通路是一条致癌通路，在多种癌症中负责细胞迁移、增殖和耐药性。在本综述中，重点阐述了PI3K/Akt信号通路在前列腺癌进展中的作用。PI3K/Akt信号通路在前列腺癌中被激活，而作为PI3K/Akt抑制剂的PTEN表达下调。PI3K/Akt信号通路的激活促进前列腺肿瘤细胞的存活并防止细胞凋亡。PI3K/Akt信号通路的诱导可增加前列腺肿瘤细胞的细胞周期进程和增殖速率。PI3K/Akt信号通路刺激上皮-间质转化并增强前列腺肿瘤细胞的转移。沉默PI3K/Akt信号通路会损害前列腺肿瘤细胞的生长和转移。PI3K/Akt信号通路的激活介导耐药性并降低前列腺肿瘤细胞的放射敏感性。抗肿瘤化合物通过抑制PI3K/Akt信号通路来阻碍前列腺肿瘤进展。此外，miRNA、lncRNA和circRNA等上游调节因子可调控PI3K/Akt信号通路，这对前列腺癌患者具有临床意义。
