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中华腔镜泌尿外科杂志(电子版) ›› 2024, Vol. 18 ›› Issue (05) : 425 -434. doi: 10.3877/cma.j.issn.1674-3253.2024.05.002

专家论坛

衰老相关分泌表型因子在前列腺癌发生发展中的作用机制
胡思平1, 熊性宇1, 徐航2, 杨璐2,()   
  1. 1. 610041 成都,四川大学华西医院泌尿外科;610041 成都,四川大学华西临床医学院
    2. 610041 成都,四川大学华西医院泌尿外科
  • 收稿日期:2024-03-29 出版日期:2024-10-01
  • 通信作者: 杨璐
  • 基金资助:
    四川省科技厅科技创新人才项目(21GJHZ0246)

The mechanisms of senescence-associated secretory phenotype factors in the occurrence and progression of prostate cancer

Siping Hu1, Xingyu Xiong1, Hang Xu2, Lu Yang2,()   

  1. 1. Department of Urology, West China Hospital of Sichuan University, Chengdu 610041, China; West China School of Clinical Medicine of Sichuan University, Chengdu 610041, China
    2. Department of Urology, West China Hospital of Sichuan University, Chengdu 610041, China
  • Received:2024-03-29 Published:2024-10-01
  • Corresponding author: Lu Yang
引用本文:

胡思平, 熊性宇, 徐航, 杨璐. 衰老相关分泌表型因子在前列腺癌发生发展中的作用机制[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2024, 18(05): 425-434.

Siping Hu, Xingyu Xiong, Hang Xu, Lu Yang. The mechanisms of senescence-associated secretory phenotype factors in the occurrence and progression of prostate cancer[J/OL]. Chinese Journal of Endourology(Electronic Edition), 2024, 18(05): 425-434.

细胞衰老可由应激损伤或生理过程引发,衰老相关分泌表型(SASP)是细胞衰老的重要表现形式。前列腺癌和正常前列腺的SASP因子包括白介素(IL-1、IL-6)、趋化因子(CXCL-8、GRO-a)、基质金属蛋白酶(MMP)家族、TNF-α、细胞间黏附分子-1(ICAM-1)等。P53、IL-1α、KDM4、ATM/HIF1α、ATM /TRAF6、MTORC1均调控了SASP。内分泌治疗、放疗、化疗均可诱导细胞衰老并发生SASP。SASP因子在前列腺癌细胞中的作用目前仍不完全清楚,尽管许多研究显示SASP因子在前列腺癌细胞存活、生长增殖、血管生成、转移、疾病进展、治疗抵抗等方面发挥了重要作用,但现有结果仍有不一致的地方,SASP因子在免疫反应上也同时具有抑制和促进的作用。并且SASP因子在其他恶性肿瘤中显示出了潜在的抑制肿瘤作用。此外,诱导前列腺癌细胞衰老是潜在的抗癌策略,多种分子均可通过诱导前列腺癌细胞衰老发挥肿瘤抑制作用,但研究显示,SASP因子诱导了前列腺正常上皮细胞系(PNT2)永生化前列腺细胞衰老,但未诱导前列腺癌细胞衰老。鉴于SASP因子在前列腺癌中的作用尚不完全清楚,并且现有的SASP因子靶向治疗临床研究仍然不足,未来应进一步加强SASP因子相关研究。

Cell senescence is triggered by stress damage or physiological processes. Senescence-associated secretory phenotype (SASP) is an important manifestation of cell senescence. SASP factors in prostate cancer and normal prostate include interleukins (IL-1, IL-6), chemokines (CXCL-8, GRO-a), matrix metalloproteinase (MMP) family, TNF-α, and intercellular adhesion molecule-1 (ICAM-1). P53, IL-1α, KDM4, ATM/HIF1α, ATM/TRAF6, and MTORC1 all regulate SASP. Endocrine therapy, radiotherapy, and chemotherapy can all induce cell senescence and lead to SASP. The role of SASP factor in prostate cancer cells is still not fully understood. Although many studies have shown that SASP factor plays an important role in prostate cancer cell survival, growth and proliferation, angiogenesis, metastasis, disease progression, and treatment resistance, there are still inconsistencies in existing results. SASP factor also has inhibitory and promoting effects on immune response. And SASP factor has shown potential anti-tumor effects in other malignant tumors. In addition, inducing prostate cancer cell senescence is a potential anti-cancer strategy, and multiple molecules can exert tumor inhibitory effects by inducing prostate cancer cell senescence. However, studies have shown that SASP factor induces PNT2 immortalized prostate cell senescence, but does not induce prostate cancer cell senescence. Given that the role of SASP factors in prostate cancer is not fully understood, and existing clinical research on SASP factor targeted therapy is still insufficient, further research on SASP factor related studies should be strengthened in the future.

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