TAMOXIFEN INDUCED CHANGES IN MCF7 HUMAN BREAST-CANCER - INVITRO AND INVIVO STUDIES USING NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPY AND IMAGING

被引:47
作者
FURMAN, E [1 ]
RUSHKIN, E [1 ]
MARGALIT, R [1 ]
BENDEL, P [1 ]
DEGANI, H [1 ]
机构
[1] WEIZMANN INST SCI,DEPT CHEM PHYS,IL-76100 REHOVOT,ISRAEL
关键词
D O I
10.1016/0960-0760(92)90207-Y
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The effects of 17-beta-estradiol versus tamoxifen on the growth and metabolism of MCF7 human breast cancer cells, in culture and in tumors implanted in nude mice, were studied by P-31 and C-13 nuclear magnetic resonance spectroscopy and by proton magnetic resonance imaging. In culture, the content of the phosphate metabolites including nucleoside triphosphates (NTP), phosphomonoesters, phosphodiesters and inorganic phosphate (Pi) were not affected by tamoxifen treatment. However, in the presence of estrogen the rate of glucose consumption and lactate production via glycolysis (270 and 280 fmol/cell . h, respectively) were twice that of tamoxifen treated cells. Estrogen rescue of tamoxifen treated cells indicated that glycolysis induction occurs at the early stages of the hormonal response. The in vivo studies included recording of proton images that provided an accurate measure of tumor size and distribution of tumor cells, necrotic regions and stromal tissue. Tamoxifen caused enhanced necrosis extending from the center of the tumor during the first two days of treatment (12 h to 6 days). This was followed by growth of reparative tissue along with tumor regression. Tamoxifen also modified the content of the phosphate metabolites, increasing markedly (P < 0.0002) the ratio of NTP to Pi from 0.41 before treatment to 1.75 9-19 days after treatment. This change was attributed to the enhanced growth of repair tissue. The results provide new information regarding the response of human breast cancer to hormonal treatment and suggest a mechanism for the induction of tumor regression by tamoxifen.
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页码:189 / 195
页数:7
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