West C M
Radiobiology Department, Paterson Institute for Cancer Research, Christie Hospital and Holt Radium Institute, Manchester, UK.
Br J Cancer. 1989 Apr;59(4):510-4. doi: 10.1038/bjc.1989.105.
Spheroids derived from the human colon adenocarcinoma cell line, WiDr, were exposed to 10 micrograms ml-1 Photofrin II and irradiated with light (700 nm, 50 mW cm-2). Compared with exponentially growing monolayer cultures, cells in spheroids of 100, 250 and 500 microns diameter were respectively 1.8, 2.5 and 22-fold less sensitive. The small resistance of plateau-phase cultures (1.3-fold) was insufficient to account for this marked spheroid size-dependent resistance. For monolayer cultures and for spheroids of 100 and 250 microns diameter, the results were the same whether irradiations were carried out pre- or post-trypsinisation. However, there was a difference for the largest spheroid size: when irradiations were carried out pre-trypsinisation, spheroids were more resistant than when irradiations were given post-trypsinisation. Drug extraction studies showed that there was no difference in the average drug uptake between cultures of exponentially growing or plateau-phase cells, and 100 microns diameter spheroids while 250 and 500 microns diameter spheroids took up proportionally 0.5 and 0.4 as much drug. Cell contact effects, drug heterogeneity between cells, hypoxia and problems in drug penetration are suggested as possible reasons for the resistance of large spheroids to photodynamic treatment.
将源自人结肠腺癌细胞系WiDr的球体暴露于10微克/毫升的二血卟啉醚，并用光（700纳米，50毫瓦/平方厘米）照射。与指数生长的单层培养物相比，直径为100、250和500微米的球体中的细胞敏感性分别低1.8、2.5和22倍。平台期培养物的小抗性（1.3倍）不足以解释这种明显的球体大小依赖性抗性。对于单层培养物以及直径为100和250微米的球体，无论胰蛋白酶消化前还是消化后进行照射，结果都是相同的。然而，对于最大的球体大小存在差异：当在胰蛋白酶消化前进行照射时，球体比在胰蛋白酶消化后进行照射时更具抗性。药物提取研究表明，指数生长或平台期细胞的培养物与直径为100微米的球体之间的平均药物摄取没有差异，而直径为250和500微米的球体摄取的药物量分别为其0.5倍和0.4倍。细胞接触效应、细胞间药物异质性、缺氧和药物渗透问题被认为是大球体对光动力治疗产生抗性的可能原因。
