Oncolytic adenovirus expressing interleukin-18 improves antitumor activity of dacarbazine for malignant melanoma

Figures & data

Figure 1 ZD55-IL-18 plus DTIC exhibited synergistic effects in the inhibition of A375 cell viability.

Notes: (A) A375 cells were treated with ZD55-IL-18 at indicated concentration for up to 4 days. (B) A375 cells were treated with DTIC at the indicated concentration for up to 4 days. (C) A375 cells were treated with ZD55-IL-18 plus DTIC, ZD55-IL-18, and DTIC at indicated concentration for up to 4 days. Cell viability was detected by MTT assay.
Abbreviations: DTIC, dacarbazine; IL-18, interleukin-18.

Figure 2 ZD55-IL-18 drove E1A and IL-18 expression in A375 cells.

Notes: Western blot analysis of E1A (A) and IL-18 (B) protein levels in A375 cells in different treatment groups.
Abbreviations: DTIC, dacarbazine; IL-18, interleukin-18; PBS, phosphate-buffered saline.

Figure 3 ZD55-IL-18 and DTIC increased apoptosis of A375 cells.

Notes: (A) At 48 hours after treatment, apoptotic cells were detected by the condensation of nuclear chromatin and its fragmentation. Magnification ×400. (B) Quantitative analysis of apoptotic A375 cells in different treatment groups. Scale bar 10 µm.
Abbreviations: DTIC, dacarbazine; PBS, phosphate-buffered saline; IL-18, interleukin-18.

Figure 4 ZD55-IL-18 and DTIC demonstrated synergistic antitumor effects in melanoma A375 mouse xenografts.

Notes: (A) Tumor growth curve of melanoma A375 xenografts in nude mice in different treatment groups. (B) Final tumor weight of melanoma A375 xenografts in nude mice in different treatment groups. *P<0.05 compared to other groups. (C) Immunohistochemical staining of IL-18 and E1A in A375 xenografts in nude mice in different treatment groups. Scale bar 5 µm.
Abbreviations: DTIC, dacarbazine; IL-18, interleukin 18; PBS, phosphate-buffered saline; w, weeks.

Figure 5 ZD55-IL-18 and DTIC demonstrated synergistic effects to induce apoptosis and upregulate VEGF expression in melanoma mouse xenografts.

Notes: (A) ZD55-IL-18 plus DTIC exhibited synergistic effects in the induction of apoptosis in melanoma A375 mouse xenografts. Tumor sections were excised and analyzed for apoptosis by TUNEL staining. Cells stained with brown granule in the nucleus were judged as apoptotic cells. (B) Immunohistochemical analysis of VEGF expression in melanoma A375 mouse xenografts is shown. (C) The lung and liver tissues were excised from nude mice in different treatment groups and analyzed by HE staining. Magnification ×400. Scale bar 5 µm. *P<0.05, **P<0.01.
Abbreviations: DTIC, dacarbazine; VEGF, vascular endothelial growth factor; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling; dUTP, 2′-deoxyuridine-5′-triphosphate; HE, hematoxylin and eosin; PBS, phosphate-buffered saline; IL-18, interleukin-18.