Abstract
Currently, new treatments are required to supplement the current standard of care for head and neck squamous cell carcinoma (HNSCC). The phosphatidylinositol3-kinase (PI3K) signaling pathway is commonly altered and activated in HNSCC. PHT-427 is a dual PI3K-mammalian target of the AKT/PDK1 inhibitor; however, to the best of our knowledge, the effect of the PHT-427 inhibitor on HNSCC has not been investigated. This study aims to evaluate the antitumoral effect of PHT-427-loaded polymeric nanoparticles based on α-tocopheryl succinate (α-TOS). The in vitro activity of PHT-427 was tested in hypopharynx carcinoma squamous cells (FaDu) to measure the cell viability, PI3KCA/AKT/PDK1 gene expression, and PI3KCA/AKT/PDK1 levels. Apoptosis, epidermal growth factor receptor (EGFR), and reactive oxygen species (ROS) were also measured. The presence of PHT-427 significantly enhances its antiproliferative and proapoptotic activity by inactivating the PI3K/AKT/PDK1 pathway. Nanoparticles (NPs) effectively suppress AKT/PDK1 expression. Additionally, NPs loaded with PHT-427 produce high oxidative stress levels that induce apoptosis. In conclusion, these results are promising in the use of this nanoformulation as a PHT-427 delivery system for effective HNSCC treatment.
Highlights
We have recently demonstrated that poly(VP-co-methacrylic derivative of α-tocopheryl succinate (MTOS)) nanoparticles loaded with α-tocopheryl succinate (α-TOS) had antitumor and antiangiogenic effects in hypopharynx squamous cell carcinoma (FaDu cells) [20,21]
Polymeric nanoparticles were successfully prepared using a MTOS11 polymer that was previously synthesized by free radical polymerization using N-vinyl pyrrolidone (VP) and a methacrylic derivative of α-TOS (MTOS) with a copolymer molar composition of VP: MTOS
In the present preclinical study, we investigated the employment of the poly(VP-co-MTOS)
Summary
Of all cancer cases worldwide, head and neck squamous cell carcinomas (HNSCC). Account for 5% [1]. Despite advances in diagnosis and treatment, HNSCC presents a poor prognosis, with a 5-year survival rate of 50–60% [1,2,3,4]. Novel agents that significantly enhance the effects of existing chemotherapeutic drugs with lower toxicity are needed. In terms of genetic aberrations, a promising pathway in HNSCC is the phosphatidylinositol 3-kinase (PI3K) signaling pathway.
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