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Combination therapy with vascular endothelial growth factor neutralizing antibody and mitomycin C on human gastric
K Matsumoto1, H Konno, T Tanaka
1Department of Surgery II, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan.
Abstract:
Antiangiogenic therapy has been proposed as a new strategy for the treatment of solid tumors. To enhance the therapeutic effect of antiangiogenic agents, combination with conventional anticancer therapy should be investigated. In the present study, we investigated the therapeutic effect of the combination of vascular endothelial growth factor neutralizing antibody (VEGF Ab) and mitomycin C (MMC) on MT-2, a human gastric cancer xenograft. When small pieces of MT-2 were transplanted orthotopically into 62 nude mice, liver metastasis developed 6 weeks after transplantation. The VEGF Ab (100 micro g / mouse) was administered i.p. in the VEGF Ab group (n = 14) and the combination group (n = 16) twice a week from day 10 after transplantation. MMC (2 mg / kg) was administered in the MMC group (n = 16) and the combination group (n = 16) on days 10, 17 and 24 after transplantation. Compared with the control group, in which saline solution was administered i.p., all three treatments inhibited tumor growth significantly and the effects of MMC and combination therapy were potent. Liver metastases were also inhibited significantly by the administration of VEGF Ab alone, MMC alone or combination therapy. Liver metastasis developed in 9 mice of the control group, 3 of the VEGF Ab group, and 4 of the MMC group, but no mice had liver metastasis in the combination therapy group. However a significant body weight loss and a decrease in spleen weight were observed in the MMC and combination groups, with no significant difference between the two groups. These results suggest that combination therapy with VEGF Ab and MMC may be a potent therapy for human gastric cancer.
Insights
Combination therapy using vascular endothelial growth factor neutralizing antibody (VEGF Ab) and mitomycin C (MMC) effectively inhibited gastric cancer growth and liver metastasis in mice. This potent combination therapy warrants further investigation for human gastric cancer treatment.
Area of Science:
- Oncology
- Cancer Research
- Pharmacology
Background:
- Antiangiogenic therapy is a promising strategy for solid tumor treatment.
- Combining antiangiogenic agents with conventional chemotherapy may enhance therapeutic effects.
- The efficacy of combining vascular endothelial growth factor neutralizing antibody (VEGF Ab) with mitomycin C (MMC) in gastric cancer requires investigation.
Purpose of the Study:
- To evaluate the therapeutic effect of combining VEGF Ab and MMC on human gastric cancer xenografts.
- To assess the impact of combination therapy on tumor growth and liver metastasis.
- To compare the efficacy of combination therapy with individual treatments and control.
Main Methods:
- Human gastric cancer (MT-2) xenografts were established in nude mice.
- Mice received VEGF Ab, MMC, combination therapy, or saline control.
- Treatments were administered over a defined period post-transplantation.
- Tumor growth, liver metastasis, body weight, and spleen weight were monitored.
Main Results:
- All treatments, including VEGF Ab alone, MMC alone, and combination therapy, significantly inhibited tumor growth compared to the control.
- Combination therapy and MMC alone demonstrated potent tumor growth inhibition.
- VEGF Ab, MMC, and combination therapy significantly reduced liver metastasis.
- No liver metastasis was observed in the combination therapy group.
- Significant body weight loss and decreased spleen weight were noted in MMC and combination groups.
Conclusions:
- Combination therapy with VEGF Ab and MMC is a potent strategy for inhibiting gastric cancer growth and liver metastasis.
- This combination therapy shows promise for treating human gastric cancer.
- Further research is needed to explore the clinical application of this combination therapy.
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