Anti‐tumor Effect of a Novel Soluble Recombinant Human Endostatin: Administered as a Single Agent or in Combination with Chemotherapy Agents in Mouse Tumor Models

Abstract

Endostatin is one of the potent anti‐angiogenesis agents, which suppress tumor formation through the inhibition of blood vessel growth. It is anticipated that combined therapy using endostatin and cytotoxic compounds may exert a synergistic effect. In the present study, we expressed and purified recombinat human endostatin (rhEndostatin) that contained 3 additional amimno acid residues (arginine, glycine, and serine) at the amino‐terminus and 6 histidine residues in its carboxyl terminus. Briefly, rhEndostatin cDNA was cloned into PQE vector and expressed in E. Coli. The protein was refolded through an optimized dialysis procedure for a large scale yield. To establish tumor models, nude mice were subcutaneously injected with human cancer cells (lung carcinoma A549, hepatocellular carcinoma QGY‐7703, or breast cancer Bcap37). For the tumor metastasis model, mice were injected intravenously with mouse melanoma B16 cells. A single dose of rhEndostatin, or in combination with CTX or DDP, was administered intravenously or at a site close to the tumor. Our results demonstrate that rhEndostatin reduced the growth of A549, QGY‐7703, and Bcap37 xenograft tumors in a dose dependent manner. When it was administered peritumorally, rhEndostatin exhibited a more potent inhibitory activity. Furthermore, rhEndostatin displayed a synergistic effect with CTX or DDP on the inhibition of metastasis of B16 tumors or growth of A549 tumors. In conclusion,soluble rhEndostatin exibibits a potent anti‐tumor activity in mouse xenograft models and it also has a synergistic effect with CTX and DDP, implying possible applications in clinical settings