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Enhancement
of radiosensitivity by tamoxifen in C6 glioma cells
Zhang W, Yamada H, Sakai N, Niikawa S, Nozawa
Y
Department of Neurosurgery, Gifu University School of Medicine,
Japan
The antiestrogen drug tamoxifen, which is used extensively in the treatment of
breast cancer, has also been reported to inhibit the proliferation of some
estrogen receptor-negative cell lines, including malignant glioma in vitro.
To
explore the possible role of tamoxifen in the treatment of malignant glioma, we
have investigated its effects on cell growth and radiosensitivity in C6 glioma
cells using a colony-forming assay and a tetrazolium-formazan growth rate assay.
Pretreatment of C6 cells with tamoxifen resulted in dose-dependent inhibition of
cell growth and enhancement of the antitumor effects of ACNU and irradiation.
The radiosensitivity of the treated cells was enhanced by the administration of
5 mumol/L of tamoxifen either before and during irradiation or continuously
before, during, and after irradiation [37% survival dose (Do) = 2.68 +/- 0.19
and 2.64 +/- 0.04 Gy, respectively, P < 0.01)], as compared with controls (Do
= 3.79 +/- 0.25 Gy).
In addition, protein kinase C activity was also inhibited
by tamoxifen at the concentration in which the radiosensitivity was augmented in
C6 cells.
Taken together, our results demonstrate a synergistic effect of
tamoxifen with radiation on intracellular damage in C6 glioma cells, which may
in part be due to the inhibition of protein kinase C, suggesting that tamoxifen
serves as a useful agent in combination therapy of glioma.
PMID: 1407459 [PubMed - indexed for MEDLINE]
Source:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1407459&dopt=Abstract
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