High-Concentration Metformin Reduces Oxidative Stress Injury and Inhibits the Growth and Migration of Clear Cell Renal Cell Carcinoma.

Objective: To explore the mechanism of metformin in treating CCRCC. Methods: Prospective cohort study was conducted. SOD and cyclin D in six CCRCC samples donated by volunteers were detected to compare the degree of oxidative stress injury and the status of cell proliferation. 786-0 CCRCC cells were cultured in vitro with different concentrations of metformin, and MTT assay and Transwell cell migration and wound healing assay were used to detect their proliferation and migration. After culture, SOD and cyclin D in 786-0 CCRCC cells were also detected. Results: In the edge tissue, SOD was lower than in the tumor nest and normal tissue, and cyclin D was highly expressed. In grade II CCRCC, SOD was higher than in grade IV CCRCC, but cyclin D was also highly expressed in grade IV CCRCC. The cell proliferation rate and density of the metformin group were lower than the control group, while in the high-concentration metformin group, it was lower than medium- and low-concentration groups. After culture, the migration of 786-0 cells in the metformin group was significantly lower than that in the control group, the wound healing rate was decreased, and the migration and wound healing rates in the high-concentration metformin group were significantly lower than those in the medium- and low-concentration groups. However, the SOD of the metformin group was higher than the control group, but the cyclin D was lower, while the SOD was higher than medium- and low-concentration groups in the high-concentration group, but the cyclin D was lower after cultured. Conclusion: High-concentration metformin can reduce oxidative stress injury, increase the expression of SOD in CCRCC, and reduce cyclin D in CCRCC to inhibit proliferation and migration, which has optimistic prospects and application value in controlling the progression of CCRCC.

Curcumin suppressed the prostate cancer by inhibiting JNK pathways via epigenetic regulation.

Curcumin is a component of turmeric and is isolated from the rhizomes of the plant Curcuma longa. Curcumin was reported to have therapeutic effects on prostate cancer. Yet the molecular mechanism of curcumin remains unclear. In this study, mouse prostate cancer xenograft model was established and subjected to curcumin treatment. GST-c-Jun pull down kinase assays were performed to study the phospho-c-Jun level. Cell Counting Kit-8 assay kit was utilized to detect the cell viability. Immunoblotting and qRT-PCR were performed for target gene expression analysis. Curcumin inhibited growth of prostate cancer in vivo as well as promoted apoptosis of LNCaP cells in vitro. Curcumin inhibited JNK pathway and repressed H3K4me3 in LNCaP cells. Combined use of curcumin and JQ-1 inhibited the prostate cancer efficiently. In conclusion, curcumin inhibits JNK pathway and plays a role in epigenetic regulation of prostate cancer cells by repressing H3K4me3.