PurposePregnane x receptor (PXR) - activated overexpression of the multidrug resistance 1 (MDR1) gene is an important way for tumor cells to acquire drug resistance. However, the detailed mechanism still remains unclear. In the present study, we aimed to investigate whether protein arginine methyl transferase 1(PRMT1) is involved in PXR - activated overexpression of MDR1 during acquired multidrug resistant.Experimental DesignArginine methyltransferase inhibitor 1 (AMI-1) was used to pharmacologically block PRMT1 in resistant breast cancer cells (MCF7/adr). The mRNA and protein levels of MDR1 were detected by real-time PCR and western blotting analysis. Immunofluorescence microscopy and co-immunoprecipitation were used to investigate the physical interaction between PXR and PRMT1. Then, 136 candidate compounds were screened for PRMT1 inhibitors. Lastly, luciferase reporter gene and nude mice bearing resistant breast cancer xenografts were adopted to investigate the anti-tumor effect of PRMT1 inhibitors when combined with adriamycin.ResultsAMI-1 significantly suppressed the expression of MDR1 in MCF7/adr cells and increased cells sensitivity of MCF7/adr to adriamycin. Physical interaction between PRMT1 and PXR exists in MCF7/adr cells, which could be disrupted by AMI-1. Those results suggest that PRMT1 may be involved in PXR-activated overexpression of MDR1 in resistant breast cancer cells, and AMI-1 may suppress MDR1 by disrupting the interaction between PRMT1 and PXR. Then, five compounds including rutin, isoquercitrin, salvianolic acid A, naproxen, and felodipline were identified to be PRMT1 inhibitors. Finally, those PRMT1 inhibitors were observed to significantly decrease MDR1 promoter activity in vitro and enhance the antitumor effect of adriamycin in nude mice that bearing resistant breast cancer xenografts.ConclusionsPRMT1 may be an important co-activator of PXR in activating MDR1 gene during acquired resistance, and PRMT1 inhibitor combined with chemotherapy drugs may be a new strategy for overcoming tumor MDR.

The incidence of ovarian cancer in women has been on the increase in recent years. The aim of the present study was to examine the effects of taxol on the expression of ovarian cancer-associated gene forkhead box transcription factor M1 (FoxM1) and its therapeutic effects for ovarian cancer. The expression of FoxM1 gene was examined in patients with or without ovarian cancer. RNA and protein levels of FoxM1 gene of ovarian cancer patients were detected at different time periods (1, 3, 6, 8, 12 and 24 months) after treatment with taxol. The results showed that the mRNA level of FoxM1 gene in patients with ovarian cancer was significantly higher than that in normal women (P<0.05). With time and progression of the disease, the expression of FoxM1 gene significantly increased in the patients not being administered taxol, whereas the expression of FoxM1 in the patients administered taxol was significantly lower comparatively (P<0.05). In conclusion, an asssociation was identified between the FoxM1 gene and ovarian cancer. The FoxM1 gene therefore promotes the generation and deterioration of ovarian cancer, whereas taxol reduces it. These findings provide a certain theoretical basis for the later treatment of ovarian cancer disease.

Abstract.Research Objective: This study aims at observing the clinical effect of the application of the lymphatic targeting drug delivery system in the treatment of malignant tumors. Research Methods: The patients with advanced gastric cancer in our hospital are taken as the samples. According to different treatment methods, they were randomly divided into two groups, namely the observation group and the control group. The patients in the control group were treated with fluorouracil, while the patients in the observation group were treated with compound fluorouracil liposome through the application of the lymphatic targeting drug delivery system in the treatment process.Research Results: In the observation group, a total of six patients experienced adverse reactions, including five patients with nausea and vomiting and one patient with leukopenia, and the incidence rate of adverse reactions was 18.75%. The patients' five-year survival rate was 75%, and the quality of life was 86.32 ± 2.09 points. Compared with the control group, the data differences were statistically significant (p<0.05). Research Conclusions: The application of the lymphatic targeting drug compound fluorouracil liposome in the treatment of gastric cancer is of great clinical value for increasing the patients' disease control rate, improving the patients' living quality and prolonging the patients' life.