Unveiling the New Trick for Epigenetic Drug: Radiation Enhancement of Prostate Cancer by the EZH2 Inhibitor...

Area of Science:

• Oncology
• Molecular Biology
• Cancer Therapeutics

Background:

• Enhancer of zeste homologue 2 inhibitor (EZH2i) Tazemetostat shows anti-tumor effects in various cancers.
• Prostate cancer (PCa) treatment can be improved with novel radiosensitizing strategies.
• Understanding EZH2 inhibition's radiosensitizing mechanisms in PCa is crucial.

Purpose of the Study:

• To evaluate the radiosensitizing potential of Tazemetostat in prostate cancer models.
• To elucidate the underlying mechanisms of Tazemetostat-induced radiosensitization.
• To assess the safety and efficacy of combining Tazemetostat with irradiation in PCa.

Main Methods:

• In vitro assays: wound healing, Transwell invasion, EdU proliferation, flow cytometry, Western blotting.
• DNA damage assessment: comet assay, γH2AX/53BP1 foci, Western blot.
• In vivo studies: mouse models, immunohistochemistry, TUNEL assay, safety evaluation.

Main Results:

• Tazemetostat plus irradiation significantly suppressed PCa cell invasion, migration, and proliferation, while increasing apoptosis.
• In vivo, the combination therapy inhibited tumor growth, reduced invasion, induced apoptosis, and extended survival.
• EZH2 inhibition enhanced radiation-induced DNA damage, increased double-strand breaks (DSBs), and impaired DSB repair.

Conclusions:

• Tazemetostat effectively enhances radiosensitivity in prostate cancer models.
• The combination therapy works by augmenting DNA damage and compromising repair mechanisms.
• These findings support the clinical translation of EZH2 inhibition as a radiosensitizing strategy for PCa patients.