Intratumoral virotherapy with Indonesian Newcastle disease virus reduces mTOR expression and induces apoptosis in rat breast cancer models

Autophagy and apoptosis are two key cellular pathways that are commonly promoted as therapeutic strategies for inhibiting cancer growth. Newcastle disease virus (NDV) has shown strong potency as cancer therapeutic agent and has been reported to induce both autophagy and apoptosis in malignant cells. NDV isolate from Indonesia has demonstrated oncolytic activity; however, the underlying mechanisms are not yet fully understood. Therefore, this study aimed to investigate the oncolytic mechanism of the Indonesian NDV isolate Tabanan-1/ARP/2017 by examining the expression of mTOR and caspase-3. Paraffin-embedded tissue blocks were obtained from a previous study. Six rats with breast cancer were divided into two groups: placebo group receiving 0.5 mL PBS, and therapy group receiving 7 log₂ HAU of NDV Tabanan-1/ARP/2017 per 0.5 mL administered intratumorally. Treatments were performed once daily for four consecutive days. After 15 days of initial treatment, the tumor tissues were collected, processed into paraffin blocks, and immunohistochemically stained with anti-mTOR and anti-caspase-3. The expression of both proteins was analyzed based on optical density using Fiji (ImageJ). mTOR expression in the therapy group was significantly lower than in the placebo group, whereas caspase-3 expression was significantly higher in the therapy group. These findings indicate that NDV Tabanan-1/ARP/2017 therapy is associated with decreased mTOR expression and apoptosis induction, as indicated by caspase-3 activation.