Li Yuanjing, Xu Shengxin, Cai Ming
Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
Institute of Atomic and Molecular Physics, Anhui Normal University, Wuhu 241000, Anhui, P.R. China.
Oncol Lett. 2018 Aug;16(2):2167-2174. doi: 10.3892/ol.2018.8911. Epub 2018 Jun 6.
The partial pressure of oxygen (PO) in the tumor microenvironment directly affects tumor sensitivity to chemotherapy. In the present study, a lithium phthalocyanine probe was implanted into MCF-7 human breast cancer cells, followed by transplant of the cells into nude mice. The present study used an electron paramagnetic resonance (EPR) oximetry measuring technique to dynamically monitor PO in the tumor microenvironment prior to and following chemotherapy, and aimed to determine the precise time window in which the microenvironmental PO peaked following chemotherapy. The results indicated that PO was significantly higher in breast cancer compared with control (P<0.05). Following four cycles of chemotherapy, the activity of NADH dehydrogenase, succinate-cytochrome reductase and cytochrome oxidase in the mitochondria of cells was significantly reduced when compared with their activity prior to chemotherapy (P<0.05). Regional blood flow in tumor tissues undergoing chemotherapy was significantly lower than that prior to chemotherapy (P<0.05). The rate of cellular apoptosis in the PO peak-based chemotherapy group was significantly greater than that in the conventional chemotherapy group after two and four cycles of chemotherapy (P<0.05). Tumor volume in the PO peak-based chemotherapy group was significantly reduced compared with that in the 0.9% NaCl solution control and the conventional chemotherapy groups after four cycles of chemotherapy (P<0.05). The tumor inhibitory rate of the experimental group was significantly higher than that of the conventional chemotherapy group (P<0.01). In conclusion, the present study may provide guidance for the development of effective strategies depending on tumor-maximal response to chemotherapy in an oxygen-rich environment. Additionally, the present study aimed to establish a foundation for a clinical noninvasive assessment intended to guide treatment and formulate individual regimens, in order to improve cancer therapeutics, sensitivity monitoring and curative effect estimation.
肿瘤微环境中的氧分压（PO）直接影响肿瘤对化疗的敏感性。在本研究中，将锂酞菁探针植入MCF-7人乳腺癌细胞，随后将细胞移植到裸鼠体内。本研究采用电子顺磁共振（EPR）血氧测定技术动态监测化疗前后肿瘤微环境中的PO，并旨在确定化疗后微环境PO达到峰值的精确时间窗。结果表明，乳腺癌中的PO显著高于对照组（P<0.05）。化疗四个周期后，与化疗前相比，细胞线粒体中NADH脱氢酶、琥珀酸-细胞色素还原酶和细胞色素氧化酶的活性显著降低（P<0.05）。接受化疗的肿瘤组织中的局部血流量显著低于化疗前（P<0.05）。在化疗两个周期和四个周期后，基于PO峰值的化疗组中的细胞凋亡率显著高于传统化疗组（P<0.05）。在化疗四个周期后，基于PO峰值的化疗组中的肿瘤体积与0.9%氯化钠溶液对照组和传统化疗组相比显著减小（P<0.05）。实验组的肿瘤抑制率显著高于传统化疗组（P<0.01）。总之，本研究可为根据肿瘤在富氧环境中对化疗的最大反应制定有效策略提供指导。此外，本研究旨在为临床无创评估建立基础，以指导治疗并制定个体化方案，从而改善癌症治疗、敏感性监测和疗效评估。
