Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
Biochem Biophys Res Commun. 2019 Jul 23;515(2):345-351. doi: 10.1016/j.bbrc.2019.05.120. Epub 2019 May 29.
Prostate cancer (PCa) is a major malignancy in men. Hitherto that date, surgical or chemical castration is the standard treatment to PCa. Nevertheless, there are still many patients with initial treatment progress to metastatic castration-resistant prostate cancer (mCRPC). There are many effective chemotherapeutic drugs for mCRPC, but the tumors will be resistant to these chemotherapeutic drugs, which is an urgent problem to be solved. Specifically, tumor therapy resistance driven by the pathologically active host stroma has gradually becoming the spotlight of oncotherapy in recent years. The exosome-derived miR-27a plays an important role in PCa cell chemoresistance. However, the functions of miR-27a on PCa developing chemoresistance remain unknown. In the present study, we aimed to construct potential regulatory networks of exosomal miR-27a in PCa chemoresistance. The expression of miR-27a was significantly increased by treatment with cisplatin, doxorubicin (DOX) and docetaxel in PCa tissues. We next co-cultured PCa cells (PC3 cells) with primary prostate fibroblasts (PSC27 cells) to explore the mechanisms of tumor therapy resistance. Further studies delineate that exosome-derived miR-27a produced by PSC-27 cells improved chemoresistance by restraining the expression of P53 gene. Our studies provide a new direction for exploring the effects of PCa tumor microenvironment of chemoresistance.
前列腺癌（PCa）是男性的主要恶性肿瘤。迄今为止，手术或化学去势仍然是治疗 PCa 的标准方法。然而，仍有许多患者在初始治疗后进展为转移性去势抵抗性前列腺癌（mCRPC）。有许多有效的化疗药物可用于 mCRPC，但肿瘤会对这些化疗药物产生耐药性，这是一个亟待解决的问题。具体来说，由病理性活跃的宿主基质驱动的肿瘤治疗耐药性已逐渐成为近年来肿瘤治疗的焦点。外泌体衍生的 miR-27a 在 PCa 细胞化疗耐药性中发挥重要作用。然而，miR-27a 在 PCa 发展化疗耐药性中的作用仍不清楚。在本研究中，我们旨在构建 PCa 化疗耐药性中外泌体 miR-27a 的潜在调控网络。顺铂、阿霉素（DOX）和多西他赛处理后，PCa 组织中 miR-27a 的表达明显增加。接下来，我们共培养 PCa 细胞（PC3 细胞）与原代前列腺成纤维细胞（PSC27 细胞），以探索肿瘤治疗耐药性的机制。进一步的研究表明，PSC-27 细胞产生的外泌体衍生的 miR-27a 通过抑制 P53 基因的表达来提高化疗耐药性。我们的研究为探索 PCa 肿瘤微环境化疗耐药性的影响提供了一个新的方向。
