Antiproliferative effect of a synthetic aptamer mimicking androgen response elements in the LNCaP cell line

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Prostate cancer often becomes hormone-refractory, resisting standard treatments.
• Androgen receptors (ARs) play a crucial role in the progression of hormone-refractory prostate cancer.
• New therapeutic strategies targeting AR signaling are essential for aggressive prostate cancer.

Purpose of the Study:

• To design a DNA aptamer (AMH) that mimics the hormone response element (HRE).
• To investigate the efficacy of AMH in inhibiting AR signaling and prostate cancer cell proliferation.
• To evaluate AMH as a potential therapeutic agent for hormone-refractory prostate cancer.

Main Methods:

• A single-stranded DNA aptamer (AMH) was designed to mimic the HRE.
• LNCaP cells (an AR-rich prostate cancer model) were used.
• Cells were transfected with AMH and treated with dehydroepiandrosterone (DHEA) at varying concentrations.
• Proliferation was compared between test, mock, and negative control groups.

Main Results:

• LNCaP cells demonstrated hormone dependency on DHEA, confirming AR pathway activity.
• AMH transfection significantly reduced LNCaP cell proliferation compared to controls.
• AMH formed a hairpin structure and competed with genomic HRE, interrupting AR signaling.

Conclusions:

• The DNA aptamer AMH effectively mimics the HRE and inhibits prostate cancer cell proliferation.
• AMH demonstrates potential as a therapeutic strategy by interrupting the androgen signaling pathway.
• This study provides a novel approach for targeting hormone-refractory prostate cancer.