柴胡皂甙-d 通过氧化磷酸化介导 FOXG1 逆转前列腺癌多西他赛耐药。
Saikosaponin-d mediates FOXG1 to reverse docetaxel resistance in prostate cancer through oxidative phosphorylation.
机构信息
Department of Urology, Wusong Central Hospital, Shanghai 200940, China.
Department of Urology, Wusong Central Hospital, Shanghai 200940, China.
出版信息
Mutat Res. 2024 Jul-Dec;829:111875. doi: 10.1016/j.mrfmmm.2024.111875. Epub 2024 Jul 23.
BACKGROUND
Prostate cancer (PCa), a prevalent malignancy worldwide, is frequently identified in advanced stages due to the absence of distinctive early symptoms, thereby culminating in the development of chemotherapy-induced drug resistance. Exploring novel resistance mechanisms and identifying new therapeutic agents can facilitate the advancement of more efficacious strategies for PCa treatment.
METHODS
Bioinformatics analysis was employed to investigate the expression of FOXG1 in PCa tissues. Subsequently, qRT-PCR was utilized to validate FOXG1 mRNA expression levels in corresponding PCa cell lines. FOXG1 knockdown was performed, and cell proliferation was assessed using CCK-8 assays, while cell migration and invasion capabilities were evaluated through wound healing and Transwell assays. Western blot and Seahorse analyzer were used to measure oxidative phosphorylation (OXPHOS) levels. Additionally, to explore potential approaches to alleviate PCa drug resistance, this study assessed the impact of biologically active saikosaponin-d (SSd) on PCa malignant progression and resistance by regulating FOXG1 expression.
RESULTS
FOXG1 exhibited high expression in PCa tissues and cell lines. Knockdown of FOXG1 inhibited the proliferation, migration, and invasion of PCa cells, while FOXG1 overexpression had the opposite effect and promoted OXPHOS levels. The addition of an OXPHOS inhibitor prevented this outcome. Finally, SSd was shown to suppress FOXG1 expression and reverse docetaxel resistance in PCa cells through the OXPHOS pathway.
CONCLUSION
This work demonstrated that SSd mediated FOXG1 to reverse malignant progression and docetaxel resistance in PCa through OXPHOS.
背景
前列腺癌（PCa）是一种全球常见的恶性肿瘤，由于缺乏明显的早期症状，常常在晚期才被发现，从而导致化疗诱导的耐药性的产生。探索新的耐药机制和寻找新的治疗药物可以促进更有效的 PCa 治疗策略的发展。
方法
利用生物信息学分析方法研究 FOXG1 在 PCa 组织中的表达情况。然后，采用 qRT-PCR 验证相应 PCa 细胞系中 FOXG1 mRNA 的表达水平。进行 FOXG1 敲低实验，通过 CCK-8 实验评估细胞增殖情况，通过划痕愈合和 Transwell 实验评估细胞迁移和侵袭能力。利用 Western blot 和 Seahorse 分析仪测量氧化磷酸化（OXPHOS）水平。此外，为了探索减轻 PCa 耐药性的潜在方法，本研究通过调节 FOXG1 表达，评估了具有生物活性的柴胡皂苷-d（SSd）对 PCa 恶性进展和耐药性的影响。
结果
FOXG1 在 PCa 组织和细胞系中表达水平较高。FOXG1 敲低抑制了 PCa 细胞的增殖、迁移和侵袭，而 FOXG1 过表达则产生相反的效果，并促进了 OXPHOS 水平。添加 OXPHOS 抑制剂可阻止这一结果。最后，SSd 被证明通过 OXPHOS 途径抑制 FOXG1 表达并逆转 PCa 细胞对多西紫杉醇的耐药性。
结论
本研究表明，SSd 通过 OXPHOS 介导 FOXG1 逆转 PCa 的恶性进展和多西紫杉醇耐药。
Zotero 插件