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Updated: Nov 11, 2025
Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
ROS production by circulating phagocytes and Guerin carcinoma resistance to cisplatin
I V Prokhorova1, O I Gorbach1, Yu R Yakshibaeva
1R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv 03022, Ukraine.
Background:
Tumor drug resistance remains a primary cause of unsuccessful cancer therapy. The search for biological markers of the sensitivity/resistance of malignant neoplasms to drug therapy is an urgent and important task, the solution of which will increase the effectiveness of anticancer chemotherapy.
Aim:
To study the relationship between the functional activity (parameters of the phagocytosis and reactive oxygen species (ROS) production) of neutrophils and monocytes in the peripheral blood of rats with transplanted Guerin carcinoma and the degree of its sensitivity to cisplatin (Cpt).
Materials And Methods:
The original and Cpt-resistant variants of Guerin carcinoma were transplanted to female Wistar rats 2.5 months old. The parameters of the phagocytic activity of circulating neutrophils and monocytes were determined by the degree of ingestion of inactivated and FITC-labeled staphylococci using flow cytometry. The number of ROS-generating cells and the intensity of ROS production by phagocytes were determined by flow cytometry using 2',7'-dichlorodihydrofluorescein diacetate.
Results:
The growth of both variants of Guerin carcinoma caused a statistically significant decrease in the intensity of neutrophil phagocytosis by more than 47% with a tendency to the reduction of the intensity of phagocytosis by monocytes. The phagocytic activity of circulating neutrophils and monocytes did not differ significantly between the groups of animals with the original and Cpt-resistant variant of Guerin carcinoma. In contrast, the intensity of ROS generation by both monocytes and neutrophils in the peripheral blood of animals with Cpt-resistant tumor increased by more than 86% as compared to original carcinoma-bearing rats.
Conclusion:
This study provides evidence that the intensity of ROS production by circulating monocytes and neutrophils may reflect the degree of tumor sensitivity to Cpt. Increased intensity of ROS production could serve as a pretreatment predictor of the formation of tumor drug resistance.
Insights
Increased reactive oxygen species (ROS) production by neutrophils and monocytes may predict tumor resistance to chemotherapy. This finding could help identify patients likely to develop drug resistance before treatment begins.
Area of Science:
- Oncology
- Immunology
- Biochemistry
Background:
- Tumor drug resistance is a major challenge in cancer therapy, necessitating the identification of predictive biomarkers.
- Understanding the mechanisms of resistance is crucial for improving the efficacy of anticancer chemotherapy.
Purpose of the Study:
- To investigate the correlation between neutrophil and monocyte functional activity and cisplatin (Cpt) sensitivity in Guerin carcinoma-bearing rats.
- To assess phagocytosis and reactive oxygen species (ROS) production as potential indicators of drug resistance.
Main Methods:
- Guerin carcinoma (original and Cpt-resistant variants) was transplanted into Wistar rats.
- Phagocytic activity of neutrophils and monocytes was measured using flow cytometry with FITC-labeled staphylococci.
- ROS production by phagocytes was quantified via flow cytometry using 2',7'-dichlorodihydrofluorescein diacetate.
Main Results:
- Tumor growth significantly reduced neutrophil phagocytosis intensity.
- Phagocytic activity of neutrophils and monocytes did not differ between original and Cpt-resistant tumor groups.
- ROS production intensity was significantly higher (over 86%) in monocytes and neutrophils of animals with Cpt-resistant tumors compared to those with original tumors.
Conclusions:
- The intensity of ROS production by circulating monocytes and neutrophils can serve as a marker for tumor sensitivity to Cpt.
- Elevated ROS production may predict the development of tumor drug resistance prior to treatment.
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