ABSTRACT
Interleukin-6 (IL-6) can promote cell proliferation in prostate cancer (PCa). Full-length transient receptor potential melastatin 2 (TRPM2-L) is highly expressed in PCa. However, the association between IL-6 and TRPM2-L in PCa is unclear. Here, human PCa cell lines, PC-3 and DU-145, were treated with 10 µg/mL tocilizumab, an IL-6 receptor (IL-6R) inhibitor, and the TRPM2-L protein expression in cells was significantly decreased. Cells were stably transfected with TRPM2 short-interfering RNA (siRNA) and cell survival clearly declined. Recombinant IL-6 treatment weakened the effects of TRPM2-siRNA on cell survival. TRPM2-L binds directly to IL-6R in PC-3 and DU-145 cells. The protein expression of hypoxia-inducible factor-1α was suppressed by reduction with TRPM2-L in PC-3 and DU-145 cells. Human umbilical vein endothelial cells (HUVECs) were indirectly cocultured with PCa cells, and the invasion and angiogenic activity of HUVECs were enhanced after coculture with PCa cells. However, TRPM2-L reduction in PCa cells significantly decreased the invasion and angiogenic activity of HUVECs compared to the control coculture. In vivo, xenograft tumors were induced using PC-3 cells. Tocilizumab treatment or TRPM2-L reduction clearly suppressed tumor growth. Meanwhile, the injection of mouse recombinant IL-6 weakened the antitumor effects of TRPM2-L reduction. These data demonstrate that the IL-6/TRPM2-L axis in PCa tumor growth is important, and interference of the IL-6/TRPM2-L axis may be a novel approach for PCa therapy.
Subject(s)
Prostatic Neoplasms , TRPM Cation Channels , Male , Humans , Animals , Mice , Interleukin-6/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , TRPM Cation Channels/genetics , TRPM Cation Channels/metabolism , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/metabolism , Human Umbilical Vein Endothelial Cells/metabolism , RNA, Small Interfering , Cell Line, TumorABSTRACT
Single-nucleotide polymorphisms in microRNAs are related to the occurrence, development and prognosis of cancer. The aim of the present study is to investigate the possible influence of the miR-499(rs3746444) polymorphism on the risk of gastric cancer in Chinese population. A total of 363 GC patients and 969 cancer-free controls were enrolled in this study. The genotypes were obtained using MassARRAY method. The results showed that, compared with T allele, C allele was associated with a significantly increased risk of GC (OR=1.491, 95% CI=1.155-1.923, P=0.002). Moreover, a significantly increased risk of GC in subjects with the TC genotype was observed (adjusted OR of 1.559, 95% CI=1.148-2.117, P=0.004), compared with the wide type TT. We also found that basically dominant model (TT vs. TC+CC) was suitable for the association between rs6513497 and the risk of GC (OR=1.568, 95% CI=1.173-2.097, P=0.002). However, the same association was also shown in males and females. Meanwhile, rs3746444 was associated with the tumor size of GC patients. The present study indicated that miR-499 rs3746444 might contribute to GC risk and this SNP could be developed as a biomarker for GC prediction.
Subject(s)
Asian People , Genotype , MicroRNAs/genetics , Polymorphism, Single Nucleotide , Stomach Neoplasms/genetics , Alleles , Case-Control Studies , China , Female , Genetic Markers , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Risk , Stomach Neoplasms/pathology , Tumor Burden/geneticsABSTRACT
AIM: To appraise the effect of sea buckthorn (Hippophae rhamnoides) on cirrhotic patients. METHODS: Fifty cirrhotic patients of Child-Pugh grade A and B were randomly divided into two groups: Group A as the treated group (n=30), taking orally the sea buckthorn extract, 15 g 3 times a day for 6 months. Group B as the control group (n=18), taking vitamin B complex one tablet, 3 times a day for 6 months. The following tests were performed before and after the treatment in both groups to determine LN, HA, collagens types III and IV, cytokines IL-6 and TNFalpha, liver serum albumin, total bile acid, ALT, AST and prothrombin time. RESULTS: The serum levels of TNFalpha, IL-6, laminin and type IV collagen in group A were significantly higher than those in the control group. After a course of sea buckthorn treatment, the serum levels of LN, HA, collagen types III and IV, total bile acid (TBA) decreased significantly as compared with those before and after treatment in the control group. The sea buckthorn notably shortened the duration for normalization of aminotransferases. CONCLUSION: Sea buckthorn may be a hopeful drug for prevention and treatment of liver fibrosis.
