关键词: 重组新城疫病毒, 新城疫病毒, Erastin, 细胞增殖, 肺腺癌

Abstract: Objective Exploration of recombinant Newcastle disease virus with stable expression of rabies virus glycoprotein(rL-RVG) to inhibit the proliferation of human lung adenocarcinoma cell lines A549 and PC9. Methods Human lung adenocarcinoma cell lines A549 and PC9 were cultured in vitro, and cells in logarithmic proliferation phase were collected and divided into control group, Newcastle disease virus infection group (NDV), recombinant Newcastle disease virus infection group(rL-RVG),ferroptosis group (Erastin) and recombinant Newcastle disease virus combined with ferroptosis inducer group (rL-RVG+Erastin). After 24 h of incubation, cell morphology was observed by microscope and cell proliferation was detected by CCK-8 method, cell migration was detected by scratch test, lactate dehydrogenase (LDH) release was measured by cytotoxicity assay kit, intracellular reactive oxygen species (ROS) content was detected by flow cytometry, and the expression of ferroptosis related proteins (p53, SLC7A11, GPX4) was detected by Western blot. Results Compared with the control group, the cell counting, cell proliferation and distance of migration were significantly reduced in the NDV group, rL-RVG group and Erastin group(P＜0.001). LDH release and total ROS level were significantly increased (P＜0.01), p53 protein expression was significantly increased(P＜0.001), while SLC7A11 and GPX4 protein expression were significantly decreased (P＜0.001). rL-RVG group had a more pronounced effect as compared with NDV group. rL-RVG+Erastin group had significantly decreased cell number, cell proliferation capacity and distance of migration compared with rl-RVG and Erastin groups(P＜0.05), and LDH release and total ROS level were significantly increased(P＜0.05), p53 protein expression was significantly increased (P＜0.001), while SLC7A11 and GPX4 protein expression were significantly decreased (P＜0.001). Conclusions rL-RVG can exert a similar effect to Erastin to inhibit tumor cell proliferation, and its effect is much stronger than that of NDV. This provides new insights into rL-RVG-induced cell death and highlights the critical role of oncolytic viruses in the treatment of tumors.

Key words: Newcastle disease virus(rL-RVG), Newcastle disease virus(NDV), Erastin, cell proliferation, lung adenocarcinoma