Salemi Souzan, Kranzbühler Benedikt, Baumgartner Valentin, Breitenmoser Lara, Kuzmanov Aleksandar, Lehner Fabienne, Eberli Daniel
Laboratory for Urologic Oncology and Stem Cell Therapy, Department of Urology, University Hospital Zürich, Wagistrasse 21, 4.OG, 8952 Schlieren, Switzerland.
Cancers (Basel). 2024 Sep 25;16(19):3261. doi: 10.3390/cancers16193261.
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.
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.
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.
These findings demonstrate that Abi + Chl treatment lowers autophagy levels and suppresses tumors more effectively than Abi alone.
阿比特龙（Abi）与泼尼松联合使用时，是晚期前列腺癌（PCa）的既定治疗方法。我们的目标是在去势小鼠异种移植模型中，探究单独使用阿比特龙治疗以及与自噬抑制剂氯喹（Chl）联合使用时所诱导的自噬水平。
将LNCaP细胞注射到先前已去势的裸鼠背部左右两侧。将小鼠分为四组，每天腹腔注射溶剂（对照）、阿比特龙（10毫克/千克）、阿比特龙（10毫克/千克）联合氯喹（10毫克/千克）或氯喹（10毫克/千克），并监测2周和3周。
与接受溶剂对照、单独使用阿比特龙或氯喹的小鼠相比，联合治疗的小鼠肿瘤重量显著降低。通过免疫荧光和全蛋白质谱分析（WES）确定，接受阿比特龙+氯喹治疗的小鼠自噬相关基因5（ATG5）、Beclin 1的表达以及微管相关蛋白轻链3（LC3）斑点减少，同时p62增加。与对照组相比，所有治疗组雄激素受体（AR）表达均显著降低。3周后，溶剂组和联合治疗组前列腺特异性膜抗原（PSMA）表达最高，氯喹治疗组PSMA表达显著降低。
这些发现表明，阿比特龙+氯喹治疗比单独使用阿比特龙更有效地降低自噬水平并抑制肿瘤。
