West C M, Moore J V
Department of Experimental Radiation Oncology, Paterson Institute for Cancer Research, Christie Hospital, Manchester, U.K.
Photochem Photobiol. 1992 Mar;55(3):425-30. doi: 10.1111/j.1751-1097.1992.tb04257.x.
The influence of cell heterogeneity on response to photodynamic treatment (PDT) has been investigated using the human colon adenocarcinoma line WiDr, grown as spheroids and exposed to hematoporphyrin derivative. The spheroids show a marked spheroid size-dependent resistance to PDT. Using a flow cytometer, cell sub-populations have been separated, on the basis of drug fluorescence, from single cell suspensions prepared from 500 microm diameter spheroids. Cells low in fluorescence have been shown to be resistant to PDT, have a smaller median cell volume, and be enhanced in G1-type cells. These cells also show reduced low density lipoprotein uptake. The results suggest that spheroid size-dependent resistance to PDT is related to a decreasing growth fraction with increasing spheroid size. Heterogeneity of drug uptake could be a potential limitation to clinical PDT.
利用人结肠腺癌系WiDr研究了细胞异质性对光动力治疗（PDT）反应的影响。WiDr细胞培养成球体，并暴露于血卟啉衍生物中。球体对PDT表现出明显的球体大小依赖性抗性。使用流式细胞仪，根据药物荧光，从直径500微米的球体制备的单细胞悬液中分离出细胞亚群。荧光低的细胞已被证明对PDT有抗性，中位细胞体积较小，且G1期细胞增多。这些细胞还表现出低密度脂蛋白摄取减少。结果表明，球体对PDT的大小依赖性抗性与球体大小增加时生长分数的降低有关。药物摄取的异质性可能是临床PDT的一个潜在限制。
