Inhibition of PI3K/AKT/mTOR pathway suppresses growth of oral squamous cell carcinoma in 2D and 3D in vitro model and animal model.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a prevalent and aggressive malignancy with a high rate of recurrence and poor prognosis. The PI3K/AKT/mTOR signaling pathway plays a pivotal role in cancer progression by regulating cell growth, survival, and metabolism. This study evaluates the therapeutic potential of targeting this pathway using in vitro (2D and 3D) and in vivo models to better mimic tumor complexity.
OBJECTIVE: OSCC cell lines (HSC3, HSC6) were treated with PI3K (LY294002), AKT (capivarsetib), and mTOR (rapamycin) inhibitors in 2D monolayers and 3D spheroids. Viability was assessed via MTT assays, and pathway modulation was confirmed by Western blot (reduced p-AKT/p-mTOR). In vivo, rapamycin's efficacy was tested in a xenograft model.
RESULTS: Pathway inhibition significantly inhibited viability and induced apoptosis in both 2D and 3D cultures, with 3D models showing differential drug sensitivity. Rapamycin suppressed tumor growth in vivo, corroborating in vitro findings.
CONCLUSION: This study supports the potential of PI3K/AKT/mTOR inhibitors as promising therapeutic agents for OSCC and underscores the need for further clinical evaluation.