Synergistic antitumor efficacy by combining adriamycin with recombinant human endostatin in an osteosarcoma model

Abstract

In the last 15 years, chemotherapy-based therapeutic regimens for the treatment of osteosarcoma have failed to demonstrate improved survival rates. Novel approaches, including targeted therapy and antiangiogenic therapy, may provide new methods for the treatment of osteosarcoma, one of the most deadly malignant diseases. In the present study, the therapeutic efficacy of an endogenous angiogenesis inhibitor, endostatin, was tested in combination with the chemotherapeutic agent, adriamycin. BALB/c mice, aged 4-6 weeks were fed animal chow and had access to water ad libitum. The mice were divided into groups and injected with tumor cells. Immunohistochemical staining was performed to identify the microvessel density. The TUNEL technique was also used to determine the apoptotic index. The combination of endostatin and adriamycin produced marked synergistic antitumor activity in a mouse osteosarcoma model. These findings provide new guidelines for designing future clinical trials and for the application of currently available clinical drugs (endostatin has been approved for clinical use) in the treatment of osteosarcoma.

Table 1. Tumor weight and tumor inhibition rate of various rh‑endostatin treatment groups.

Table 2. Combination treatment of rh‑endostatin with adriamycin FTW^a relative to controls.

Table 3. MVD of various treatment groups.

Figure 1. (A) Tissue stained with hematoxylin and eosin is shown and the nuclear pleomorphism of malignant tumor feature is evident (arrow). (B) Intratumoral vascular endothelium cells were stained by rabbit anti-Fac VIII (arrow). Tumor tissue with (D) high-dose rh-endostatin treatment alone showed fewer new vascular endothelium cells than the (C) control. (B-D) were counterstained with hematoxylin.

Table 4. AI of various treatment groups.

Figure 2. Combination treatment of high-dose (B) rh‑endostatin and adriamycin showed more apoptotic tumor cells than the (A) control. (C) and (D) show that apoptotic foci were often concentrated within the perivascular areas in the combination treatment groups