Cancer cell spheroids as a model to evaluate chemotherapy protocols
Cancer cell spheroids as a model to evaluate chemotherapy protocols
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DOI：
10.4161/cbt.21353
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发表时间：
2012-10-01
影响因子：
3.6
通讯作者：
Torchilin, Vladimir P.
中科院分区：
文献类型：
--
作者：
Perche, Federico;Torchilin, Vladimir P.
为了确定球状体培养物是否可用于评价药物疗效，我们使用耐药癌细胞的球状体培养物评价了游离或载体相关多柔比星作为单一药物或与其他抗癌剂联合的毒性。紫杉醇、顺铂、地塞米松、米托蒽醌、香紫苏醇或甲氨蝶呤与多柔比星联合使用。分别通过荧光和乳酸脱氢酶释放评价治疗方案对游离、胶束和脂质体阿霉素在球状体中蓄积以及对所产生毒性的影响。米托蒽醌或紫杉醇预处理后，观察到增加阿霉素蓄积和毒性。与阿霉素联合用药的效果是顺序依赖性的，使用阿霉素作为第一种药物是最小的毒性诱导剂。最后，球状体被癌细胞特异性抗体识别。我们的研究结果表明，球体的有用性，以评估化疗组合。
To determine whether the spheroid culture can be used to evaluate drug efficacy, we have evaluated the toxicity of free or carrier-associated doxorubicin as a single drug or in combination with other antineoplastic agents using the spheroid cultures of drug-resistant cancer cells. Paclitaxel, cisplatin, dexamethasone, mitoxantrone, sclareol or methotrexate were used in combination with doxorubicin. The effect of the treatment protocols on free, micellar and liposomal doxorubicin accumulation in spheroids and on resulting toxicity was evaluated by fluorescence and lactate dehydrogenase release, respectively. Enhanced doxorubicin accumulation and toxicity were observed after spheroid pretreatment with mitoxantrone or paclitaxel. Effects of the drug combination with doxorubicin were sequence dependent, use of doxorubicin as the first drug being the least inducer of toxicity. Finally, spheroids were recognized by a cancer cell-specific antibody. Our results suggest the usefulness of spheroids to evaluate chemotherapy combinations.