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Quantitative Analysis of Autophagy using Advanced 3D Fluorescence Microscopy

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Simultaneous Autophagy and Androgen Receptor Inhibition in a Prostate Cancer Xenograft Model.

Souzan Salemi¹, Benedikt Kranzbühler¹, Valentin Baumgartner¹

¹Laboratory for Urologic Oncology and Stem Cell Therapy, Department of Urology, University Hospital Zürich, Wagistrasse 21, 4.OG, 8952 Schlieren, Switzerland.

|October 16, 2024

Summary

Combining abiraterone (Abi) with chloroquine (Chl) significantly reduces prostate cancer tumor growth by inhibiting autophagy. This combination therapy is more effective than Abi alone in a castrated mouse model.

Keywords:

PSMA abiraterone autophagy in vivo prostate cancer

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Published on: August 28, 2013

Area of Science:

Oncology
Molecular Biology
Pharmacology

Background:

Abiraterone (Abi) is an established treatment for advanced prostate cancer (PCa), often used with prednisone.
Autophagy plays a role in cancer progression and treatment resistance.
Understanding autophagy modulation by Abi is crucial for optimizing PCa therapy.

Purpose of the Study:

To investigate the level of autophagy induced by Abi treatment alone and in combination with the autophagy inhibitor chloroquine (Chl).
To evaluate the efficacy of Abi and Chl combination therapy in a castrated mouse xenograft model of PCa.

Main Methods:

LNCaP cells were xenografted into castrated nude mice.
Mice were treated with vehicle, Abi, Abi + Chl, or Chl.
Tumor weight, autophagy markers (ATG5, Beclin 1, LC3, P62), AR, and PSMA expression were analyzed.

Main Results:

Combination therapy (Abi + Chl) significantly reduced tumor weight compared to monotherapy or vehicle control.
Abi + Chl treatment decreased autophagy markers (ATG5, Beclin 1, LC3) and increased P62.
Androgen receptor (AR) expression decreased across all treatment groups; Prostate-specific membrane antigen (PSMA) expression was highest in vehicle and combination groups at 3 weeks.

Conclusions:

Abi + Chl treatment effectively lowers autophagy levels in prostate cancer xenografts.
The combination of Abi and Chl demonstrates superior tumor suppression compared to Abi alone.