Donson A M, Weil M D, Foreman N K
University of Colorado Health Sciences Center, Denver, USA.
J Neurosurg. 1999 Mar;90(3):533-6. doi: 10.3171/jns.1999.90.3.0533.
A combined tamoxifen and radiation therapy is being used in clinical trials to treat glioblastoma multiforme (GBM). The rationale behind this therapy is that tamoxifen is a radiosensitizer. However, the evidence for this is weak. The authors, therefore, examined the effect of combined radiation-tamoxifen therapy in three GBM cell lines of human origin.
The GBM cell lines were exposed to different concentrations (0.3-5 microg/ml) of tamoxifen and subsequently irradiated at varying doses (0.8-5 Gy). Tumor growth inhibition was measured using a proliferation assay. The interaction of tamoxifen and radiation therapies was quantified using the combination index method, which distinguishes whether a combined antitumor effect is synergistic, additive, or antagonistic. At high doses of tamoxifen or radiation there was significant inhibition of tumor cell proliferation. At low doses of either therapeutic agent, there was little effect. In one cell line, synergism occurred at high doses of tamoxifen and radiation. In the other two cell lines, an additive effect was observed. In only one of the three cell lines was there synergy between tamoxifen and radiation at doses that significantly inhibited tumor proliferation.
Because synergy could not be demonstrated in all three cell lines at active dosages, the clinical combination of tamoxifen and radiation therapies may not be of benefit to all patients.
他莫昔芬与放射治疗联合应用于多形性胶质母细胞瘤（GBM）的临床试验。该治疗方法的理论依据是他莫昔芬是一种放射增敏剂。然而，支持这一观点的证据并不充分。因此，作者研究了他莫昔芬与放射治疗联合应用对三种人源GBM细胞系的影响。
将GBM细胞系暴露于不同浓度（0.3 - 5微克/毫升）的他莫昔芬中，随后给予不同剂量（0.8 - 5戈瑞）的辐射。使用增殖试验测量肿瘤生长抑制情况。采用联合指数法对他莫昔芬与放射治疗的相互作用进行量化，该方法可区分联合抗肿瘤效应是协同、相加还是拮抗。高剂量的他莫昔芬或辐射可显著抑制肿瘤细胞增殖。低剂量的任何一种治疗药物效果都不明显。在一种细胞系中，高剂量的他莫昔芬与辐射产生协同作用。在另外两种细胞系中，观察到的是相加效应。在三种细胞系中，只有一种在显著抑制肿瘤增殖的剂量下，他莫昔芬与辐射之间存在协同作用。
由于在有效剂量下并非所有三种细胞系都能证明存在协同作用，他莫昔芬与放射治疗的临床联合应用可能并非对所有患者都有益。
