Fig 6. Anti-angiogenic activity of [NSIS6S]-[NSIS]₅ in combination with cisplatin in ovarian cancer model.

A to D, six tumor xenografts were established from ES2 ovarian cancer cell line in each treatment group. ES2 tumor-bearing mice were treated for 7 days with saline (daily), cisplatin (10 mg/kg, once a week) and a combination of cisplatin and bevacizumab (15 mg/kg, twice a week) or sunitinib (40 mg/kg, daily) (A); saline, bevacizumab and sunitinib as single agents at doses indicated in A (B); saline, cisplatin (10 mg/kg, once a week) and a combination of cisplatin and [NSIS6S]-[NSIS]₅ (160 mg/kg, b.i.d.) (C); saline and [NSIS6S]-[NSIS]₅ as a single agent at 160 mg/kg b.i.d. (D). *, P < 0.05. E, Tumor sections were stained with antibodies against murine CD31 and SMAα to visualise vasculature and perivascular mural cells, respectively. Scale bars, 200 μm. F to I, microvascular density (F), number of vessels with lumen (G), average vessel size (H) and vessel maturity (I) were determined using Definiens software which analyzed images of tumor sections immunostained for CD31 and SMAα. Vessel maturity was determined as a percentage of CD31- and SMAα-positive blood vessels. The data are expressed as the mean ± SEM (n = 6). *, P < 0.05.