关键词: 电子顺磁共振, 肿瘤微环境, 氧分压, 乳腺癌

Abstract:

Background and purpose: Tumor microenvironment plays an important role in the introduction of foreign factors that mediate tumor acquired resistance. The antitumor effects of many chemotherapeutic agents depend on the level of oxygen pressure (pO₂) in tumor microenvironment. This study aimed to evaluate electron paramagnetic resonance (EPR)-based monitoring on an oxygen-enriched tumor microenvironment to increase chemotherapeutic sensitivity. Methods: MCF-7 cells were used to establish human breast cancer in nude mice. EPR was used to directly measure pO₂ level in vivo. Tumor tissues were collected, and mitochondrial activity was assayed on the basis of the kinetics of enzyme-catalyzed reactions. A laser Doppler monitor was used to detect regional blood flow. Tumor apoptotic rate was analyzed by flow cytometry. Results: The tumor volume decreased more evidently in the chemotherapy group with oxygen- enriched environment than that in the conventional chemotherapy group after the treatment was administered (P<0.01). After chemotherapy was completed, the apoptotic rate of tumor cells was significantly higher in the chemotherapy group with oxygen-enriched environment than that in the conventional chemotherapy group (P<0.001). This study examined the mechanism of pO₂ changes in tumor microenvironment: This was related to the change of the balance between the oxygen consumption and the regional blood flow in the tumor tissues after chemotherapy. Conclusion: Based on the characteristics of pO₂ changes in the tumor microenvironment after chemotherapy was completed, the selection of chemotherapy mode for the treatment in pO₂ peak time window improves the sensitivity of chemotherapy, which provides a new idea for individualized chemotherapy in clinical applications.

Key words: Electron paramagnetic resonance, Tumor microenvironment, pO₂, Breast cancer