Morphological changes in the ovarian carcinoma cells of Wistar rats induced by chemotherapy with cisplatin and dioxadet.

A A Zhikhoreva,A L Semenov,V G Bespalov,I V Semenova,N T Zhilinskaya,G V Tochilnikov,O S Vasyutinskii,A V Belashov

doi:10.1364/boe.9.005817

A A Zhikhoreva, A L Semenov + Show 6 more

Open Access

https://doi.org/10.1364/boe.9.005817

Copy DOI

Journal: Biomedical optics express	Publication Date: Oct 29, 2018
Citations: 18	License type: cc-by

Affiliation: Institute of Oncology NN Petrov

Abstract

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..

Highlights

Ovarian cancer is one of most frequent cancers, ranking fifth in cancer deaths among women
In this paper digital holographic microscopy and tomography were used for determination of a number of morphological parameters of cells that were shown to change dramatically in the course of chemotherapy depending on the cell type and agent applied
We have demonstrated the essential difference in morphology of both normal and cancerous cells in the ascitic fluid taken from the non-treated group of rats and the groups treated with DOD and CPC

Summary

Introduction

Ovarian cancer is one of most frequent cancers, ranking fifth in cancer deaths among women. Specific chemicals or in phase-contrast microscopes, allow to visually determine and evaluate changes in cellular morphology These measurements provide data on a nuclear area, membrane area, nucleus to cytoplasm ratio, optical density of a nucleus that is associated with DNA content, see e.g. The recently developed 3D imaging techniques implementing optical computed tomography allow for investigating nuclear morphology and texture in 3D with sub-micron spatial resolution [7] This technology still operates with distributions of absorption coefficient and requires specific sample preparation using dyes and fixation agents. In this paper digital holographic microscopy and tomography were used for determination of a number of morphological parameters of cells (average phase shift, volume, membrane area) that were shown to change dramatically in the course of chemotherapy depending on the cell type and agent applied. The conclusions made were shown to be in agreement with recent results on the analysis of these cytostatics efficacy evaluated by experimentally determined survival rates of rats exposed to chemotherapy with these agents [33]

Experimental approach

Experimental methodology

Findings

Conclusions