Liposomal Azd5363 Displays Antiproliferation Activities and Induces Apoptosis on Y79 Retinoblastoma Cancer Cells Publisher



Khabazian Z¹ ; Esmaeil N^{2, 3} ; Khanehzad M¹ ; Majd AHN¹ ; Tohidian M⁴ ; Zarinfard G¹ Show Affiliations
Source: South Asian Journal of Cancer Published:2024

Abstract

Objectives Retinoblastoma (RB) is an aggressive intraocular cancer that usually develops during infancy and childhood. As an Akt kinase inhibitor, AZD5363 is a novel drug whose encapsulation into liposomes enhances its bioavailability and biomedical potential. In the present study, a liposomal membrane was created around AZD5363 to assess its efficacy on the Y79 cancer cell line. Materials and Methods AZD5363 nanoparticles were synthesized by the thin film hydration method. Dynamic light scattering (DLS) and field emission scanning electron microscopy (FESEM) techniques were applied to evaluate the particle size, and the morphology of the liposomal AZD5363 (Lipo-AZD5363). The MTT test was used to assess the half maximal inhibitory concentration (IC50) of Lipo-AZD5363, and the cytotoxic effects of Lipo-AZD5363 and doxorubicin (Dox) were investigated on the Y79 cell line. Flow cytometry was used to study apoptotic induction in selected groups. Also, the PTEN/AKT/FOXO1 gene expression level was measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay. Results Treatment with Lipo-AZD5363 inhibited the proliferation of Y79 RB cancer cell line in a dose-dependent manner. Lipo-AZD5363, at a lower concentration, was significantly more cytotoxic than Dox in terms of enhanced cell death (p < 0.05). Furthermore, flow cytometry showed that Lipo-AZD5363 and Dox induce apoptosis in these cells. However, the number of apoptotic cells in the Lipo-AZD5363 group was clearly higher than that in the Dox group (p < 0.001). Real-time PCR analysis indicated that Lipo-AZD5363 treatment resulted in an increase in PTEN and FOXO1 gene expression and a decrease in AKT gene expression. Our study revealed that all results were statistically more significant in the Lipo-AZD5363 group than in the Dox group (p < 0.01, <0.01, and <0.001, respectively). Conclusion Lipo-AZD5363 inhibits proliferation and promotes apoptosis of RB cells by inhibiting the PI3K/AKT signaling pathway. Thus, Lipo-AZD5363 may be a promising candidate for cancer therapy. However, more experimental evidence is needed for its use in the pharmacological treatment of RB. © 2024. MedIntel Services Pvt Ltd. All rights reserved.