Fig. 4.
Prodrug 8 suppresses 4T1 tumor growth and lung metastasis. (A) In vivo effect of prodrug 8 on 4T1 mammary carcinoma. Starting on day 5, when the tumors averaged ≈ 4 mm in diameter, the 4T1 tumor mice were treated with 0.5, 1.5 and 3 mg/kg of the prodrug 8 separately on day 5, 8, 11, 14 and 17. without any toxicity, but 3 mg/kg dosage of prodrug 3 caused mouse death. 6 mice were treated in each group; (p<0.001). (B) Prodrug 8 treatment induces cell death in TUNEL staining of 4T1 tumor sections. (C) Prodrug 8 suppresses spontaneous lung metastasis in 4T1 mouse breast cancer models (p<0.001). (D) Legumain activity of tumor tissue is significantly higher than that of normal tissues. The experiments were repeated in three mice (p<0.01).