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Effects of recombinant human endostatin on a human neuroblastoma xenograft
1Department of Surgery, Gunma Children's Medical Center, Hokkitsu, Seta-gun, Gunma 377-8577, Japan.
Abstract:
New antitumor agents must be added to the current neuroblastoma treatment regimens to improve the clinical results. We investigated whether recombinant human endostatin (rhEndostatin), an antiangiogenic agent, is effective against human neuroblastoma in the human neuroblastoma xenograft model designated TNB9. When tumors on the back of nude mice grew to a weight of 90-95 mg, rhEndostatin 10 mg/kg/day was administered subcutaneously every day for 10 consecutive days. Mean relative tumor weight in mice administered rhEndostatin (n=5) was significantly less than that in controls (n=12) on days 2, 4, and 6 after the start of administration (p<0.01 on day 2, p<0.05 on days 4 and 6), and regression of tumor growth (TRW<1.0) was marked on day 2. The maximum inhibition rate (MIR) by rhEndostatin was 46.4%, indicating inefficacy, but it may not be appropriate to apply Battelle Columbus Laboratories criteria to this experimental model because rhEndostatin is a protein. After day 8, tumors in the experimental group increased in weight and were not statistically significantly different from those in controls. Recombinant human endostatin was used in tumors in the arterial system of the mouse in this experiment because eventually rhEndostatin, not recombinant mouse endostatin, may be used to treat advanced neuroblastoma in the clinical setting. The results show that there is little cross-reactivity of rhEndostatin with the human and mouse models and indicate that rhEndostatin could become an effective agent for the treatment of human neuroblastoma.
Insights
Recombinant human endostatin showed initial promise in inhibiting neuroblastoma tumor growth in mice. However, its efficacy waned, suggesting limited cross-reactivity and potential for treating human neuroblastoma.
Area of Science:
- Oncology
- Pharmacology
- Biotechnology
Background:
- Neuroblastoma treatment requires novel antitumor agents to improve outcomes.
- Antiangiogenic agents, such as endostatin, are explored for cancer therapy.
Purpose of the Study:
- To evaluate the efficacy of recombinant human endostatin (rhEndostatin) against human neuroblastoma.
- To assess rhEndostatin's potential as a treatment for advanced neuroblastoma.
Main Methods:
- A human neuroblastoma xenograft model (TNB9) in nude mice was utilized.
- rhEndostatin (10 mg/kg/day) was administered subcutaneously for 10 consecutive days.
- Tumor weight and regression were monitored and compared between treated and control groups.
Main Results:
- rhEndostatin significantly reduced mean relative tumor weight on days 2, 4, and 6 post-administration.
- Marked tumor growth regression was observed on day 2, with a maximum inhibition rate of 46.4%.
- Tumor growth in the experimental group was not statistically different from controls after day 8.
Conclusions:
- rhEndostatin demonstrated transient anti-tumor activity in the neuroblastoma xenograft model.
- Limited cross-reactivity between human and mouse models suggests rhEndostatin's potential for human neuroblastoma treatment.
- Further investigation is warranted to optimize rhEndostatin therapy for clinical application.