Antimetastatic activities of pegylated liposomal doxorubicin in a murine metastatic lung cancer model

Abstract

To determine whether pegylated liposomal doxorubicin (PLD) could control the metastasis beyond primary tumor, the efficacy of PLD was evaluated in terms of metastatic growth inhibition and increasing life span in a murine lung metastasis model. As early as 20 days after C57BL/6 mice were inoculated with 2 × 106 murine Lewis lung carcinoma cells into the right legs, metastases could be observed in the lungs. Comparing the metastatic status of the PLD treatment conducted one day with one week after the tumor implantation, pathological study of the metastasis in the lungs indicated that without the removal of primary tumor, PLD could prevent metastasis by suppressing the growth of primary tumor. To evaluate the direct antimetastasis ability of PLD with clinical relevance, a surgery was performed to resect the tumor-bearing limb. The treatment was started 3 days after the amputation with free doxorubicin or PLD. In this therapeutic model, PLD targeted directly to the metastasis in the lungs, which resulted in substantially longer survival time than free doxorubicin. Despite the superiority of PLD over free doxorubicin in treating pulmonary metastasis, our observation suggested that without the removal of primary tumor, the effect of PLD was only modest, and surgery plus multiple injections of PLD will be the best choice for patients with metastatic disease.