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Published on: August 12, 2015
Silencing APLNR enhances the radiosensitivity of prostate cancer by modulating the PI3K/AKT/mTOR signaling pathway
Peng Li1, Yanfang Cui2, Keyao Hu1
1Department of Urology, Yantaishan Hospital, Laishan District Science and Technology Avenue 10087, Yantai, 264003, Shandong, People's Republic of China.
Background:
Aberrant expression of apelin receptor (APLNR) has been found to be involved in various cancers' development, however, its function in prostate cancer (PCa) remains unclear. The research aimed to investigate the role and potential mechanism of APLNR in PCa.
Methods:
The mRNA expression of APLNR was detected via qRT-PCR assay. PCa cell proliferation and apoptosis were determined through plate cloning and flow cytometry. In addition, the expression of apoptosis-related proteins (Bax, Bcl-2, and cleaved caspase-3) was evaluated using western blot. DNA damage marker (γ-H2AX) was analyzed by immunofluorescence and western blot. GSEA analysis was performed for seeking enrichment pathways of APLNR in PCa, and the protein levels of PI3K, p-PI3K, AKT, p-AKT, mTOR, and p-mTOR were tested using western blot.
Results:
APLNR expression was up-regulated in PCa tissues and cells. Silencing APLNR enhanced the sensitivity of PCa cells to radiotherapy, which was manifested by inhibiting cell proliferation, promoting cell apoptosis, and promoting DNA damage. Next, silencing APLNR inhibited the PI3K/AKT/mTOR pathway. Specifically, 740Y-P (the PI3K/AKT/mTOR pathway activator) reversed the effects of silencing APLNR on PCa cell proliferation, apoptosis and DNA damage.
Conclusion:
Silencing APLNR inhibited cell proliferation, promoted cell apoptosis, and enhanced the radiosensitivity of PCa cells, which was involved in the PI3K/AKT/mTOR signaling pathway. This study is conducive to the deeper understanding of PCa and further provides a new perspective for the treatment of PCa.
Insights
Silencing the apelin receptor (APLNR) in prostate cancer (PCa) inhibits proliferation and promotes apoptosis, enhancing radiosensitivity. This effect is mediated by the PI3K/AKT/mTOR pathway, offering new therapeutic strategies for PCa.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Aberrant apelin receptor (APLNR) expression is implicated in various cancers.
- The specific role of APLNR in prostate cancer (PCa) pathogenesis is not well understood.
- This research investigates the function and underlying mechanisms of APLNR in PCa.
Purpose of the Study:
- To elucidate the role of apelin receptor (APLNR) in prostate cancer (PCa).
- To explore the potential molecular mechanisms by which APLNR influences PCa progression.
- To assess the impact of APLNR modulation on PCa cell behavior and radiosensitivity.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) for APLNR mRNA expression.
- Cell proliferation assays (plate cloning) and apoptosis analysis (flow cytometry).
- Western blot for apoptosis-related proteins (Bax, Bcl-2, cleaved caspase-3) and PI3K/AKT/mTOR pathway components; immunofluorescence for DNA damage marker (γ-H2AX).
Main Results:
- APLNR expression is significantly upregulated in PCa tissues and cells.
- Silencing APLNR inhibited PCa cell proliferation, induced apoptosis, and promoted DNA damage, enhancing radiosensitivity.
- APLNR silencing suppressed the PI3K/AKT/mTOR pathway; pathway activation reversed these effects.
Conclusions:
- Downregulation of APLNR inhibits PCa cell proliferation and apoptosis while enhancing radiosensitivity.
- The observed effects are linked to the modulation of the PI3K/AKT/mTOR signaling pathway.
- Targeting APLNR presents a novel therapeutic strategy for prostate cancer treatment.
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