Fig. 1 | Signal Transduction and Targeted Therapy

Fig. 1

From: Non-small cell lung cancers (NSCLCs) oncolysis using coxsackievirus B5 and synergistic DNA-damage response inhibitors

Fig. 1

Screening of an oncolytic virus and its anti-tumor effects in multiple tumor models. a Non-small cell lung cancer cells (NSCLCs; A549, NCI-H1299, NCI-H460), hepatocarcinoma cells (Hep3B, HepG2, PLC/PRF/5), cervical carcinoma cells (HeLa) were infected with CV-B3/Nancy, CV-B5/Faulkner (CV-B5/F), CV-A6/Gdula at an MOI of 1, 0.1, 0.01 for 48 h. Cell viability was assessed by CCK8 assay. b–g NCI-H1299 (n = 5, b), A549 (n = 5, d), and NCI-H460 (n = 5, f) cells were subcutaneously injected into the right flank of BALB/c nude mice. Each mouse received five doses of CV-B5/F intratumorally when the diameter of the tumor reached 4–5 mm. Tumor volumes are expressed as mean ± SEMs. *P < 0.05; **P < 0.01. Kaplan–Meier survival analyses were performed for CV-B5/F-treated mice with five doses (c: NCI-H1299; e: A549; g: NCI-H460). h, i Administration of CV-B5/F to the right tumor (h: NCI-H1299, n = 5; i: A549, n = 5) was performed in BALB/c nude mice with bilateral tumors. *, $P < 0.05; **, $$P < 0.01. Each symbol represents the statistical significance of the right and left lateral tumors between untreated and treated mice. j, k NCI-H1299 cells expressing firefly luciferase were subcutaneously injected into the axillia of BALB/c nude mice (n = 4). The bioluminescent images were measured using the IVIS-Lumina II imaging system on days 2, 4, 6, 8, 10, and 12. Relative bioluminescence intensity is shown in pseudocolor, with red representing the strongest and blue representing the weakest photon fluxes (j). The bioluminescence intensities of control and CV-B5/F-treated mice are shown as mean ± deviation (k). l, m NCI-H1299 was combined with Matrigel at a 1:1 ratio immediately before subcutaneous injection into the axillia of B-NDG mice. Seven days after treatment, PBMCs were injected intraperitoneally in PBS. On day 10, tumors were dissected for immunohistochemistry (IHC) using anti-CD4 and CD8 antibodies. Numbers of positive cell in high-power field (n = 20) were analyzed. One-way ANOVA was used to analyze the data. Scale bars, 100 μm. ****P < 0.0001. n Tumor volume curves of patient-derived xenografts (PDX) for NSCLC after treatment with five doses of CV-B5/F

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