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Antiangiogenic and antitumor effects of tranilast on mouse lung carcinoma cells
J Yatsunami1, S Aoki, Y Fukuno
1Department of Internal Medicine, Saga Medical School, Saga 849-8501, Japan. yatsunam@post.saga-med.ac.jp
Abstract:
We examined the effects of tranilast on tumor angiogenesis, tumor growth and metastasis in the mouse Lewis lung carcinoma and C57BL mouse system. Tranilast significantly reduced the dense capillary network induced by Lewis lung cancer cells in a mouse dorsal air sac angiogenesis model. Intraperitoneal administration of tranilast at 200 mg/kg/day reduced the tumor size of mouse Lewis lung carcinoma to about 63% of that of the control and suppressed pulmonary metastasis in a spontaneous system. Immunohistochemistry revealed that tranilast reduced the tumor vascularity and increased apoptosis of the tumor cells in vivo. Tranilast potentiated the inhibition of the tumor growth induced by cyclophosphamide, cis-diamminedichloroplatinum(II), adriamycin and vindesine in vivo. These results suggest that tranilast has antiangiogenic and antitumor effects and might have possible therapeutic applications.
Insights
Tranilast demonstrated significant anti-tumor effects by inhibiting angiogenesis and reducing tumor growth and metastasis in mouse models. This drug also enhanced the efficacy of conventional chemotherapy agents.
Area of Science:
- Oncology
- Pharmacology
- Cancer Biology
Background:
- Tumor angiogenesis is crucial for tumor growth and metastasis.
- Developing effective anti-cancer therapies targeting angiogenesis is a key research area.
- Tranilast is a known anti-allergic drug with potential anti-cancer properties.
Purpose of the Study:
- To investigate the anti-angiogenic and anti-tumor effects of tranilast.
- To evaluate tranilast's impact on tumor growth and metastasis in Lewis lung carcinoma models.
- To assess tranilast's potential in combination therapy with chemotherapeutic agents.
Main Methods:
- Utilized a mouse dorsal air sac angiogenesis model to assess capillary network formation.
- Administered tranilast intraperitoneally at 200 mg/kg/day in Lewis lung carcinoma mouse models.
- Employed immunohistochemistry to analyze tumor vascularity and cell apoptosis in vivo.
- Evaluated tranilast's efficacy in combination with cyclophosphamide, cisplatin, adriamycin, and vindesine.
Main Results:
- Tranilast significantly reduced the dense capillary network in the angiogenesis model.
- Tranilast administration suppressed Lewis lung carcinoma tumor size by approximately 37% and inhibited pulmonary metastasis.
- Immunohistochemistry confirmed reduced tumor vascularity and increased tumor cell apoptosis.
- Tranilast potentiated the anti-tumor effects of standard chemotherapeutic drugs.
Conclusions:
- Tranilast exhibits significant anti-angiogenic and anti-tumor properties.
- Tranilast effectively reduces tumor growth, vascularity, and metastasis.
- Tranilast shows promise as a therapeutic agent, particularly in combination with chemotherapy.
