Scholarlink

Background <p>Retinoblastoma is a pediatric intraocular cancer usually driven by RB1 gene mutations, with Y79 cells serving as a retinoblastoma model bearing RB1 inactivation. Paraoxonases (PON1, PON2, PON3) are antioxidant proteins; PON1 is HDL-associated, whereas PON2 and PON3 are intracellular, with PON2 localized to the inner mitochondrial membrane. The PI3K/Akt pathway is a key survival cascade frequently hyperactivated in cancer. This study evaluated PON isoform expression in Y79 retinoblastoma cells and examined whether their regulation is mediated by PI3K/Akt signaling.</p> Methods <p>Adult Retinal Pigment Epithelial (ARPE-19), Human Retinal Endothelial Cells (HREC), Human Retinal Pericytes (HRP), and Y79 cells were cultured under standard conditions, serum-starved, and treated with the Akt pathway inhibitor LY294002 (5 &amp; 10 µM). Gene expression was assessed using quantitative real-time PCR. Protein expression of Akt, phosphorylated Akt (p-Akt), and PON2 was analyzed by Western blotting. Statistical analyses were performed using one-way ANOVA, and data were expressed as mean ± SEM.</p> Results <p>Our results showed that the expression of PON1 was increased; PON2 and PON3 were decreased in Y79 cells when compared with HREC, and ARPE-19. The expression of p-Akt was elevated in Y79 cells, and LY294002 decreased the expression of p-Akt and PON1 and PON3 without altering PON2 mRNA expression, indicating that there is differential regulation of PON genes in Y79 cells and is regulated by the PI3K/Akt pathway.</p> Conclusion <p>These findings indicate that PI3K/Akt signaling sustains a pro-survival, antioxidant phenotype in retinoblastoma cells through selective regulation of PON isoforms, highlighting this pathway as a promising therapeutic target.</p> Graphical abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

PI3K inhibition modulates PON gene expression and disrupts survival pathways in retinoblastoma Y-79 cells

  • 期刊论文

  • 发表日期：

    2026年4月17日

查看全文
  • Ramya Ravi,
  • Sathik Shajahan,
  • Jayavigneeswari Suresh babu,
  • S. R. Bharathi devi

摘要

Background

Retinoblastoma is a pediatric intraocular cancer usually driven by RB1 gene mutations, with Y79 cells serving as a retinoblastoma model bearing RB1 inactivation. Paraoxonases (PON1, PON2, PON3) are antioxidant proteins; PON1 is HDL-associated, whereas PON2 and PON3 are intracellular, with PON2 localized to the inner mitochondrial membrane. The PI3K/Akt pathway is a key survival cascade frequently hyperactivated in cancer. This study evaluated PON isoform expression in Y79 retinoblastoma cells and examined whether their regulation is mediated by PI3K/Akt signaling.

Methods

Adult Retinal Pigment Epithelial (ARPE-19), Human Retinal Endothelial Cells (HREC), Human Retinal Pericytes (HRP), and Y79 cells were cultured under standard conditions, serum-starved, and treated with the Akt pathway inhibitor LY294002 (5 & 10 µM). Gene expression was assessed using quantitative real-time PCR. Protein expression of Akt, phosphorylated Akt (p-Akt), and PON2 was analyzed by Western blotting. Statistical analyses were performed using one-way ANOVA, and data were expressed as mean ± SEM.

Results

Our results showed that the expression of PON1 was increased; PON2 and PON3 were decreased in Y79 cells when compared with HREC, and ARPE-19. The expression of p-Akt was elevated in Y79 cells, and LY294002 decreased the expression of p-Akt and PON1 and PON3 without altering PON2 mRNA expression, indicating that there is differential regulation of PON genes in Y79 cells and is regulated by the PI3K/Akt pathway.

Conclusion

These findings indicate that PI3K/Akt signaling sustains a pro-survival, antioxidant phenotype in retinoblastoma cells through selective regulation of PON isoforms, highlighting this pathway as a promising therapeutic target.

Graphical abstract