Recombinant Newcastle virus rL-RVG inhibits proliferation of human lung adenocarcinoma cell lines

doi:10.16352/j.issn.1001-6325.2023.10.1549

Abstract

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

CLC Number:

R734.2

ZHANG Zhenzhen, LI Yang, GAO Shengbao, XIA Dexin, YAN Yulan. Recombinant Newcastle virus rL-RVG inhibits proliferation of human lung adenocarcinoma cell lines[J]. Basic & Clinical Medicine, 2023, 43(10): 1549-1556.

0
/ / Recommend

Add to citation manager EndNote|Reference Manager|ProCite|BibTeX|RefWorks

URL: http://journal11.magtechjournal.com/Jwk_jcyxylc/EN/10.16352/j.issn.1001-6325.2023.10.1549

http://journal11.magtechjournal.com/Jwk_jcyxylc/EN/Y2023/V43/I10/1549

References

[1]Hyuna S,Jacque F,Siegel J,et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA,2021,71: 209-249.
[2]Altorki N, Markowitz G, Gao D, et al. Lung microenvironment:an important regulator of tumour metastasis[J]. Nat Rev Cancer, 2019: 19: 9-31.
[3]Petersen I. The morphological and molecular diagnosis of lung cancer[J]. Dtsch Arztebl Int, 2011, 108: 525-531.
[4]Xie Y,Zhu S,Song X,et al. The tumor suppressor p53 limits ferroptosis by blocking DPP4 activity[J]. Cell Rep,2017,20: 1692-1704.
[5]Dixon SJ,Lemberg KM,Lamprecht MR,et al. Ferroptosis:an iron-dependent form of nonapoptotic cell death[J]. Cell,2012,149: 1060-1072.
[6]Tang D,Chen X,Kang R,et al. Ferroptosis:molecular mechanisms and health implications[J]. Cell Res,2021,31: 107-125.
[7]徐飞,陈维达,郭溟浩等.铁死亡调控机制及在肺癌治疗中的研究进展[J].基础医学与临床,2021,41: 442-447.
[8]Mansour M,Palese P,Zamarin D. Oncolytic specificity of Newcastle disease virus is mediated by selectivity for apoptosis-resistant cells[J]. J Virol,2011,85: 6015-6023.
[9]Kan X,Yin Y,Song C,et al. Newcastle-disease-virus-induced ferroptosis through nutrient deprivation and ferritinophagy in tumor cells[J]. iScience,2021,24: 1028-1037.
[10]Sun LL, Linghu DL, Hung MC. Ferroptosis: a promising target for cancer immunotherapy[J]. Am J Cancer Res, 2021, 11: 5856-5863
[11]Liu W, Chen H, Zhu Z, et al. Ferroptosis inducer improves the efficacy of oncolytic virus-mediated cancer immunotherapy[J]. Biomedicines, 2022, 10: 1425.doi: 10.3390/biomedicines10061425.
[12]Lang FF,Conrad C,Gomez-Manzano C,et al. Phase Ⅰ study of DNX-2401 (Delta-24-RGD) oncolytic adeno-virus: replication and immunotherapeutic effects in recur-rent malignant glioma[J]. J Clin Oncol,2018,36: 1419-1427.
[13]Chai Z,Zhang P,Fu F,et al. Oncolytic therapy of a recombinant Newcastle disease virus D90 strain for lung cancer[J]. Virol J,2014,11: 84.doi: 10.1186/1743-422X-11-84.
[14]Zhao M,Gao Y,Wang L,et al.Overexpression of integrin-linked kinase promotes lung cancer cell migration and invasion via NF-κB-mediated upregulation of matrix metalloproteinase-9[J]. Int J Med Sci,2013,10: 995-1002.
[15]Yan Yl,Jia Lj,Zhang J,et al. In vivo effect of recombinant newcastle disease virus transfection on lung adenocar-cinoma A549 cells[J]. Oncol Lett,2014,8: 2569-2576.
[16]Wu Y,Song J,Wang Y,et al. The potential role of ferroptosis in neonatal brain injury[J]. Front Neurosci,2019,13: 115.doi: 10.3389/fnins.2019.00115.