ABSTRACT
The resistance and dose limitation of tumors is a serious obstacle to cytotoxic drug therapy in the field of medical oncology. Nitric oxide (NO) is a powerful adjuvant for tumor hypersensitivity for traditional chemotherapy and radiation therapy. The concentration of NO plays an important role in affecting its anti-tumor effect. This review summarizes the mechanism of concentration-dependent effects of NO on tumor cells and the mechanism of chemotherapy sensitization. It provides evidence for rational use of NO to exert anti-tumor effects, and overcoming multidrug resistance and anti-tumor drug development.
ABSTRACT
Objective@#To observe the effect of miR-17-92 overexpression on the chemosensitivity of leukemia mice and the chemosensitivity of compound Zhebei granules.@*Methods@#The miR-17-92 over-expressed cells and L1210 cells were conventionally infused into each DBA/2N mouse through the vena caudalis at the cellular concentration of 100×104. The mice were divided into 5 groups with a randomized method, including miR-17-92 high expression L1210 cell leukemia mice (miR-17-92) observation group, miRNA-17-92 chemotherapy group, miRNA-17-92 chemotherapy combined with compound Zhebei granules group, L1210 chemotherapy group and normal control group. The chemotherapy groups were given cyclophosphamide by intraperitoneal injection, or chemotherapy combined with compound Zhebei granules group plus compound Zhebei. In the course of the experiment, the routine blood and white blood cell classification were checked every 7 days. The animals were killed on the 15th day or before dying. Peripheral blood routine and white blood cell classification were detected, the proportion of leukemia cells was checked by using bone marrow morphology. Furthermore, it was necessary to weigh the spleen and observe histopathological changes. P-glycoprotein (P-gp) expression was detected by using enzyme-linked immunosorbent assay.@*Results@#The difference between hemoglobin and platelet count on the 15th day after administration was statistically significant in the miRNA-17-92 observation group, miRNA-17-92 chemotherapy group, miRNA-17-92 chemotherapy combined compound Zhebei group, L1210 chemotherapy group, and normal control group (F= 5.76, P= 0.002; F= 16.90, P= 0.002); Compared with the normal control group, peripheral blood leukocyte count in the miRNA-17-92 observation group was decreased (P < 0.05). The proportion of peripheral blood leukemic cells was (37.2±13.1)%, (5.7±1.9)%, (1.3±0.8)%, (0.8±0.3)%, 0, and the proportion of myeloid leukemia cells was (26.9±11.0)%, (6.8±2.0)%, (3.2±1.0)%, (1.7±1.2)%, 0, and the difference was statistically significant (F= 24.38, P= 0.000 0; F= 19.71, P= 0.000 0). The spleen weights were (0.70±0.18), (0.20±0.07), (0.44±0.17), (0.23±0.19), (0.60±0.18) g respectively, and the difference was statistically significant (F= 8.78, P= 0.032). Chemotherapy could reduce leukemia spleen infiltration. P-gp was (33±11), (27±11), (32±11), (20±11), (17±3) ng/ml, and the difference was statistically significant (F= 10.42, P= 0.034). Compound Zhebei granules did not significantly reduce P-gp expression.@*Conclusions@#The overexpression of miRNA-17-92 leads to the decrease of chemotherapy response rate. Compound Zhebei granules combined with chemotherapy could improve the response rate of miR-17-92 high expression L1210 mice.