Figure 5.

MDK inhibitor exhibits anti-tumor and anti-metastasis effects on a xenograft mouse model of NSCLC. (A) H1299 cells were transfected with E.V. and Myc-DDK-MDK, which were selected by G418 (400 μg/mL) until colony formation. H1299 cells were injected subcutaneously into nude mice 1 × 10⁶ cells/mouse, and tumor formation was measured every 3 days for 60 days from day 7 after implantation. Groups were intraperitoneally treated: DMSO (100 μL/ 1 time/ 2 days) in the control and iMDK (9 mg/ kg/ 1 time/ 2 days) in the drug treated-groups. Student’s t test was performed and values displayed as average ±SEM; n = 10, * p < 0.05. (B) Tumor weight was measured after removal. Student’s t test was performed and values displayed as average ±SEM; n = 10, * p < 0.05. (C) Tumor xenograft images, hematoxylin and eosin (H&E), and immunohistochemical staining of anti-MDK, anti-T antigen, and CD-31 in mice tumors from each group. (Scale bar: 25/ 50/ 100 μm). (D) Lung metastasis observed in lung tumor images and histological H&E staining of tissue sections from DMSO and drug-treated group (Scale bar: 100 μm). (E) Top: quantification of the incidence of mice with lung metastasis in the control, MDK, and MDK+iMDK-treated group. Bottom: contingency table relating the number and percentage of mice in each treatment or metastasis case. iMDK treated-mice showed a statistically significant decrease in the incidence of lung metastasis based on the chi-square test (n = 10, * p < 0.05).