Scheduling of chemotherapy based on direct monitoring ofpO2 in tumor microenvironment by EPR oximetry / 中国癌症杂志

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 reso-nance (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 levelin 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 oxy-gen-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 ofpO2 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 ofpO2 changes in the tumor microenvironment after chemotherapy was completed, the selection of chemotherapy mode forthe treatment inpO2 peak time window improves the sensitivity of chemotherapy, which provides a new idea for individual-ized chemotherapy in clinical applications.