Metronomic treatment of temozolomide inhibits tumor cell growth through reduction of angiogenesis and augmentation of apoptosis in orthotopic models of gliomas
- Authors
- Kim, JT[Kim, JT]; Kim, JS[Kim, JS]; Ko, KW[Ko, KW]; Kong, DS[Kong, DS]; Kang, CM[Kang, CM]; Kim, MH[Kim, MH]; Son, MJ[Son, MJ]; Song, HS[Song, HS]; Shin, HJ[Shin, HJ]; Lee, DS[Lee, DS]; Eoh, W[Eoh, W]; Nam, DH[Nam, DH]
- Issue Date
- Jul-2006
- Publisher
- PROFESSOR D A SPANDIDOS
- Citation
- ONCOLOGY REPORTS, v.16, no.1, pp.33 - 39
- Indexed
- SCIE
SCOPUS
- Journal Title
- ONCOLOGY REPORTS
- Volume
- 16
- Number
- 1
- Start Page
- 33
- End Page
- 39
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/87039
- ISSN
- 1021-335X
- Abstract
- Glioblastoma is a highly angiogenic tumor with a dismal prognosis. Temozolomide (TMZ), a methylating agent is one of the most effective chemotherapeutic agents against glioblastoma. To overcome the problem that most of these tumors become resistant to chemotherapeutic regimens within a year, we investigated the antitumor efficacy of metronomic administration of low-dose TMZ in in vitro cell proliferation/cytotoxicity assay and in vivo rat and nude mouse orthotopic glioma model. By in vitro assay, we elucidated that C6/LacZ rat glioma cells were more resistant to metronomic treatment of TMZ than U-87MG human glioblastoma cells and bEnd.3 mouse brain endothelial cells. Compared with the conventional chemotherapeutic regimen of TMZ, we found that frequent administration of TMZ at a low dose (metronomic treatment) markedly inhibited angiogenesis as well as tumor growth in a TMZ-resistant C6/LacZ rat glioma model. In addition, metronomic treatment of TMZ significantly augmented apoptosis of tumor cells in this model. For the TMZ-sensitive U-87MG cells, even with a very low dose of TMZ, which is not effective to reduce tumor mass, the metronomic treatment of TMZ reduced the microvessel density, i.e. angiogenesis, in a nude mouse orthotopic model. In conclusion, for both models, the metronomic treatment of TMZ decreased angiogenesis. Especially, in TMZ-resistant glioma cells, this regimen increased apoptosis of tumor cells and decreased tumor growth. The metronomic treatment of TMZ in orthotopic glioma models demonstrated a successful antiangiogenic effect which can overcome the chemoresistance in conventional TMZ chemotherapy.
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Collections - Medicine > Department of Medicine > 1. Journal Articles
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