13-顺式维甲酸与α2a干扰素联合使用对人宫颈癌细胞的体外放射增敏作用
In vitro radiosensitization of human cervical carcinoma cells by combined use of 13-cis-retinoic acid and interferon-alpha2a.
作者信息
Ryu S, Kim O B, Kim S H, He S Q, Kim J H
机构信息
Department of Radiation Oncology, State University of New York Health Science Center, Syracuse 13210, USA.
出版信息
Int J Radiat Oncol Biol Phys. 1998 Jul 1;41(4):869-73. doi: 10.1016/s0360-3016(98)00111-4.
BACKGROUND
Significant antitumor activity has been reported with the combined use of 13-cis-retinoic acid (cRA) and interferon-alpha2a (IFN-alpha) in the treatment of advanced-stage cervical cancers and skin cancers. Since IFN-alpha has been shown to be a modest radiation enhancer for selected malignant tumor cells and the cytotoxic activity is more enhanced by combining cRA and IFN-alpha, we hypothesized that the exposure of selected human carcinoma cells to combined cRA and IFN-alpha would render the cells highly radiosensitive.
METHODS AND MATERIALS
Two human cervical carcinoma cell lines, ME-180 and HeLa-S3, were chosen for the present study because of the different characteristics of the retinoic acid receptor status of the cell lines. To demonstrate the effects of combined cRA and IFN-alpha treatment on radiation response, we exposed the cells to cRA, IFN-alpha, or a combination of the drugs for 72 h before radiation. Experiments were carried out at minimally cytotoxic concentrations of the drug for radiation studies. End points of the study were cell growth inhibition and clonogenic ability of the single-plated cells. Effects of cRA and IFN-alpha on radiation response were quantitatively analyzed by constructing the radiation cell survival curves of ME-180 and HeLa cells.
RESULTS
ME-180 cells exhibited varying degrees of cytotoxicity with cRA and IFN-alpha, while HeLa cells showed no toxic effects with the same treatment. Combined treatment of cRA and IFN-alpha produced an additive cytotoxic effect in ME-180 cells. Radiosensitization was minimal when ME-180 cells were treated with either cRA or IFN-alpha before radiation. When ME-180 cells were exposed to 10 microM cRA for 48 h and 1000 U/ml IFN-alpha for 24 h prior to radiation, there was a significant enhancement in radiation-induced cell killing; the dose modification factor was 2.1 +/- 0.9 at the 1% cell-survival level. On the other hand, HeLa-S3 cells exhibited no increased cytotoxicity or radiation enhancement under the same experimental conditions.
CONCLUSION
The present data provide a radiobiological basis for using cRA and IFN-alpha as a combination radiosensitizer in selected human carcinoma cells.
背景
据报道，13-顺式维甲酸（cRA）与干扰素-α2a（IFN-α）联合使用在晚期宫颈癌和皮肤癌治疗中具有显著的抗肿瘤活性。由于IFN-α已被证明是某些恶性肿瘤细胞的适度辐射增强剂，且cRA与IFN-α联合使用时细胞毒性活性增强更明显，我们推测将某些人癌细胞暴露于cRA与IFN-α联合环境中会使细胞具有高度放射敏感性。
方法与材料
由于这两种细胞系视黄酸受体状态的不同特性，本研究选择了两个人宫颈癌细胞系ME-180和HeLa-S3。为了证明cRA与IFN-α联合处理对辐射反应的影响，我们在辐射前将细胞暴露于cRA、IFN-α或这两种药物的组合中72小时。实验在药物对辐射研究的最小细胞毒性浓度下进行。研究的终点是细胞生长抑制和单细胞平板接种的克隆形成能力。通过构建ME-180和HeLa细胞的辐射细胞存活曲线，定量分析cRA和IFN-α对辐射反应的影响。
结果
ME-180细胞对cRA和IFN-α表现出不同程度的细胞毒性，而HeLa细胞在相同处理下未显示出毒性作用。cRA与IFN-α联合处理在ME-180细胞中产生了相加的细胞毒性作用。在辐射前用cRA或IFN-α处理ME-180细胞时，放射增敏作用最小。当ME-180细胞在辐射前暴露于10微摩尔/升的cRA 48小时和1000国际单位/毫升的IFN-α 24小时时，辐射诱导的细胞杀伤有显著增强；在1%细胞存活水平下，剂量修正因子为2.1±0.9。另一方面，在相同实验条件下，HeLa-S3细胞未表现出细胞毒性增加或辐射增强。
结论
目前的数据为在某些人癌细胞中使用cRA和IFN-α作为联合放射增敏剂提供了放射生物学依据。
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