Objective: Abi, when used in conjunction with prednisone, is an established treatment for advanced PCa. Our goal was to explore the level of autophagy induced by Abi treatment, both alone and in combination with the autophagy inhibitor Chl, in a castrated mouse xenograft model. Methods: LNCaP cells were injected into the left and right sides of the back of nude mice that had been previously castrated. Mice were divided into four groups and treated daily with intraperitoneal injections of vehicle (control), Abi (10 mg/kg), Abi (10 mg/kg) combined with Chl (10 mg/kg), or Chl (10 mg/kg), and were monitored for periods of 2 and 3 weeks. Results: A significant reduction in tumor weight was observed in mice treated with the combination therapy, as opposed to those receiving vehicle control, Abi, or Chl alone. Mice receiving Abi + Chl exhibited reduced expression of ATG5, Beclin 1, and LC3 punctuations, along with an increase in P62, as determined by immunofluorescence and WES analysis. AR expression decreased significantly in all treatment groups compared to the control. PSMA expression was highest in the vehicle and combined treatment groups after 3 weeks, with a significant reduction observed with Chl treatment. Conclusions: These findings demonstrate that Abi + Chl treatment lowers autophagy levels and suppresses tumors more effectively than Abi alone.
目的：阿比特龙联合泼尼松是晚期前列腺癌的标准治疗方案。本研究旨在探索去势小鼠异种移植模型中，阿比特龙单药及其联合自噬抑制剂氯喹治疗所诱导的自噬水平。方法：将LNCaP细胞注射至预先去势的裸鼠背部左右两侧，将小鼠分为四组，每日腹腔注射给药：溶剂对照、阿比特龙（10 mg/kg）、阿比特龙（10 mg/kg）联合氯喹（10 mg/kg）、氯喹单药（10 mg/kg），分别观察2周和3周。结果：联合治疗组小鼠肿瘤重量较溶剂对照、阿比特龙单药或氯喹单药组显著降低。免疫荧光与WES分析显示，阿比特龙联合氯喹治疗组小鼠肿瘤组织中ATG5、Beclin 1表达及LC3点状聚集减少，P62表达增加。所有治疗组的雄激素受体表达均较对照组显著下降。治疗3周后，溶剂对照组与联合治疗组的前列腺特异性膜抗原表达最高，而氯喹单药组该表达显著降低。结论：本研究表明，阿比特龙联合氯喹治疗较阿比特龙单药能更有效降低自噬水平并抑制肿瘤生长。
Simultaneous Autophagy and Androgen Receptor Inhibition in a Prostate Cancer Xenograft Model
肿瘤(癌症)患者之家