A sulindac analogue is effective against malignant pleural effusion in mice

Abstract

Objectives To examine whether a sulindac derivative (C-18) with previously reported anti-angiogenic properties limits malignant pleural effusion (MPE) formation in mice. Methods MPE was generated by intrapleural injection of murine adenocarcinoma cells in C57BL/6 mice. Animals were divided into three groups, a control group and two treatment groups receiving intraperitoneally a daily dose of either 1 mg or 2 mg of C-18 for a total of 12 doses. Mice were sacrificed on day 14. Measurements and main results Pleural fluid volume and the number of pleural tumor implantations were measured. Tumor angiogenesis, pleural vascular permeability and the host inflammatory response were also assessed. C-18 significantly limited pleural fluid formation and inhibited intrapleural tumor dissemination. The mean ± SEM pleural fluid volume was 758 ± 63 μl for the control group, compared to 492 ± 120 μl ( p = 0.042) and 279 ± 77 μl ( p < 0.001) for the low dose and high dose group of C-18, respectively. Control group animals had 6.2 ± 1 intrapleural tumors, while C-18 treated animals had 3.1 ± 0.8 ( p = 0.014) and 3 ± 0.7 ( p = 0.009) for the low and high dose respectively. In addition C-18 significantly suppressed pleural vascular permeability. No significant difference in tumor angiogenesis and inflammatory response was observed, while there was also no measurable effect in tumor cell apoptosis and proliferation in vitro and in vivo. Conclusions C-18 halted experimental MPE formation and intrapleural tumor dissemination, through down-regulation of pleural vascular permeability.