Zhikhoreva A A, Belashov A V, Bespalov V G, Semenov A L, Semenova I V, Tochilnikov G V, Zhilinskaya N T, Vasyutinskii O S
Ioffe Institute; 26 Polytekhnicheskaya, St.Petersburg, 194021, Russia.
ITMO University; Kronverkskiy pr., 49, St. Petersburg, 197101, Russia.
Biomed Opt Express. 2018 Oct 29;9(11):5817-5827. doi: 10.1364/BOE.9.005817. eCollection 2018 Nov 1.
The development of new express methods for the analysis of the efficacy of anti-cancer therapy on the cellular level is highly desirable for the analysis of chemotherapeutic agent performance. In this paper we suggest the use of parameters of cell morphology determined by holographic microscopy and tomography for the effective label free quantitative analysis of cell viability under antitumor chemotherapy and thus of cytostatic agent efficacy. As shown, measured phase shifts and cell morphology change dramatically as a result of chemotherapy and depend strongly on the cell type and agent applied. Experimentally, a comparative analysis of the antitumor efficacy of the two cytostatics, cisplatin and dioxadet, that are commonly used for chemotherapy of disseminated ovarian carcinoma has been performed. The experiments were carried out on the Wistar rat model. An essential difference in the morphology of cells, both normal (erythrocytes) and cancerous, present in ascitic fluid taken from the non-treated group of rats and the groups treated with either dioxadet or cisplatin, has been observed. The results obtained can be interpreted as an indication of the antitumor performance of both cytostatics at the cellular level and as a demonstration of the higher efficacy of therapy with dioxadet as compared to that with cisplatin. Differences in cell morphology are suggested to be applied as quantitative markers of cell viability and cytostatic agent efficacy. The conclusions made are supported by a comparison with the results of recent experiments based on survival rates of laboratory animals treated with these agents..
开发用于在细胞水平分析抗癌治疗效果的新快速方法，对于分析化疗药物性能而言是非常必要的。在本文中，我们建议使用通过全息显微镜和断层扫描确定的细胞形态参数，来对抗肿瘤化疗下的细胞活力进行有效的无标记定量分析，从而分析细胞抑制剂的疗效。结果表明，化疗会导致测量的相移和细胞形态发生显著变化，并且强烈依赖于细胞类型和所应用的药物。通过实验，对两种常用于播散性卵巢癌化疗的细胞抑制剂顺铂和二恶烷的抗肿瘤疗效进行了比较分析。实验在Wistar大鼠模型上进行。观察到从未经治疗的大鼠组以及用二恶烷或顺铂治疗的组采集的腹水中存在的正常细胞（红细胞）和癌细胞的形态存在本质差异。所获得的结果可以解释为这两种细胞抑制剂在细胞水平上的抗肿瘤性能的指标，以及表明二恶烷治疗比顺铂治疗具有更高的疗效。细胞形态的差异被建议用作细胞活力和细胞抑制剂疗效的定量标记。通过与基于用这些药物治疗的实验动物存活率的近期实验结果进行比较，支持了所得出的结论。
