Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia.
Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia; Malaysia Genome and Vaccine Institute, National Institutes of Biotechnology Malaysia, Jalan Bangi, 43000, Kajang, Selangor, Malaysia.
Virology. 2024 Feb;590:109957. doi: 10.1016/j.virol.2023.109957. Epub 2023 Dec 7.
Newcastle disease virus (NDV) is an oncolytic virus which selectively replicates in cancer cells without harming normal cells. Autophagy is a cellular mechanism that breaks down unused cytoplasmic constituents into nutrients. In previous studies, autophagy enhanced NDV-induced oncolysis in lung cancer and glioma cells. However, the effect of autophagy inhibition on NDV-induced oncolysis in breast cancer cells remains unknown. This study aimed to examine the effect of autophagy inhibition on NDV-induced oncolysis in human breast cancer cells, MCF7. To inhibit autophagy, we knocked down the expression of the autophagy protein beclin-1 (BECN1) by short interfering RNA (siRNA). The cells were infected with the recombinant NDV strain AF2240 expressing green fluorescent protein. We found that NDV induced autophagy and knockdown of BECN1 significantly reduced the NDV-induced autophagy in MCF7 cells. Importantly, BECN1 knockdown significantly suppressed cell death by inhibiting viral replication, as observed at 24 h post infection. Overall, our data suggest that autophagy inhibition may not be a suitable strategy to enhance NDV oncolytic efficacy against breast cancer.
新城疫病毒（NDV）是一种溶瘤病毒，它能够选择性地在癌细胞中复制，而不会伤害正常细胞。自噬是一种细胞机制，它将细胞质中未使用的成分分解为营养物质。在以前的研究中，自噬增强了 NDV 诱导的肺癌和神经胶质瘤细胞的溶瘤作用。然而，自噬抑制对 NDV 诱导的乳腺癌细胞溶瘤作用的影响尚不清楚。本研究旨在探讨自噬抑制对 NDV 诱导的人乳腺癌细胞 MCF7 溶瘤作用的影响。为了抑制自噬，我们通过短发夹 RNA（siRNA）敲低自噬蛋白 beclin-1（BECN1）的表达。细胞用表达绿色荧光蛋白的重组 NDV 株 AF2240 感染。我们发现，NDV 诱导自噬，并且 BECN1 的敲低显著减少了 MCF7 细胞中的 NDV 诱导的自噬。重要的是，BECN1 的敲低通过抑制病毒复制显著抑制了细胞死亡，这在感染后 24 小时观察到。总的来说，我们的数据表明，自噬抑制可能不是增强 NDV 溶瘤效力对抗乳腺癌的合适策略。
