Knockdown of membrane-bound complement regulatory proteins suppresses colon cancer growth in mice through inducing tumor cell apoptosis.

CD46, CD55 and CD59 are membrane-bound complement regulatory proteins (mCRPs) and highly expressed in many tumor tissues. Our analysis by RNA sequencing and qRT-PCR revealed that the expression of mCRPs was significantly elevated in cancer tissues of 15 patients with colon cancer. To further investigate the role of mCRPs in the development of colon cancer, we suppressed the expression of mCRPs by CD46-shRNA, CD55-shRNA and CD59-shRNA in colon cancer cell lines, SW620 and HT-29 cells. The results indicated that CD46-shRNA, CD55-shRNA and CD59-shRNA effectively reduced the expression of mCRPs, accompanied with the increased LDH release and the percentage of Annexin V + 7-AAD- early phase of apoptotic cells. The similar cytotoxic effects were also observed in the cells treated with CD46 neutralizing antibody (aCD46), associated with the increased C5b-9 deposition, cleaved caspase-3 and Bax expression in the treated cells. The cytotoxic effects by mCRPs knock-down were potentiated in the cells co-treated with doxorubicin (Dox). In addition, STAT3, STAT6, and p38 MAPK inhibitors, including C188-9, AS1517499 and SB203580 effectively reduced the expression of CD46 in the treated colon cells, associated with increased cell apoptosis and LDH release. Further study with mouse model revealed that mCRPs knockdown by mCRPs-shRNA significantly reduced colon cancer growth, associated with increased expression of Bax, cleaved caspase-3 and C5b-9 deposition, but reduced expression of Bcl-2, IL-6 and IL-1beta in tumor tissues of nude mice transplanted with SW620 cells. Thereby, mCRPs expression in human colon cancer cells were upregulated by STAT3/STAT6/p38 MAPK signaling and mCRPs knockdown reduced colon cancer growth in mice through inducing tumor cell apoptosis.

Gastrointestinal Cancers and Liver Cirrhosis: Implications on Treatments and Prognosis.

Liver cirrhosis tends to increase the risk in the management of gastrointestinal tumors. Patients with gastrointestinal cancers and liver cirrhosis often have serious postoperative complications and poor prognosis after surgery. Multiple studies have shown that the stage of gastrointestinal cancers and the grade of cirrhosis can influence surgical options and postoperative complications. The higher the stage of cancer and the poorer the degree of cirrhosis, the less the surgical options and the higher the risk of postoperative complications. Therefore, in the treatment of patients with gastrointestinal cancer and liver cirrhosis, clinicians should comprehensively consider the cancer stage, cirrhosis grade, and possible postoperative complications. This review summarizes the treatment methods of patients with different gastrointestinal cancer complicated with liver cirrhosis.

MicroRNA-31 Function as a Suppressor Was Regulated by Epigenetic Mechanisms in Gastric Cancer.

Gastric cancer is one of the most lethal malignancies worldwide. The aberrant expression of microRNA-31 (miR-31) has been reported in gastric cancer; however, its regulation mechanisms are still unclear. Here, we confirmed that miR-31 expression was significantly decreased in gastric cancer tissue and cell lines. Ectopic expression of miR-31 potentially suppresses proliferation and induced early apoptosis in gastric cancer cells. Furthermore, miR-31 expression was regulated as a result of epigenetic mechanisms. The downregulation of miR-31 was associated with promoter DNA methylation status in gastric cancer and cell lines. Moreover, we found that HDAC2 was the direct target of miR-31 by binding to 3'-UTR from the results of luciferase reporter assays, qRT-PCR, and western blotting. HDAC2 played an activation role in tumor growth, whose expression is upregulated and inversely associated with miR-31 levels. All the results suggested that miR-31 function as a crucial tumor suppressor was regulated by epigenetic mechanisms in gastric cancer. We found an epigenetic pathway loop, DNA methylation-miRNA expression-target gene-tumor progression in gastric cancer, and also provided implications for molecular diagnosis and therapeutics of gastric malignancies by detecting miR-31 as a potential target.

Thiazolidione derivatives targeting the histidine kinase YycG are effective against both planktonic and biofilm-associated Staphylococcus epidermidis.

AIM: To evaluate the efficacies of six derivatives of Compound 2, a novel YycG histidine kinase inhibitor with the thiazolidione core structure in the treatment of medical device-related biofilm infections. METHODS: The minimal inhibitory concentration (MIC) of the derivatives was determined using the macrodilution broth method, and the minimal bactericidal concentration (MBC) was obtained via sub-culturing 100 µL from each negative tube from the MIC assay onto drug-free Mueller-Hinton agar plates. Biofilm-killing effect for immature (6 h-old) biofilms was examined using a semiquantitative plate assay, and the effect on mature (24 h-old) biofilms was observed under a confocal laser scanning microscope (CLSM). RESULTS: The derivatives potently suppressed the growth of Staphylococcus epidermidis. The MIC values of the derivatives H2-10, H2-12, H2-20, H2-29, H2-27, and H2-28 on S epidermidis ATCC 35984 were 24.3, 6.5, 6.2, 3.3, 3.1, and 1.5 µg/mL, respectively. The MBC values of these derivatives were 48.6, 52.2, 12.4, 52.6, 12.4, and 6.2 µg/mL, respectively. The derivatives killed all bacteria in immature (6 h-old) biofilms and eliminated the biofilm proliferation. The derivatives also displayed strong bactericidal activities toward cells in mature (24 h-old) biofilms, whereas they showed low cytotoxicity and hemolytic activity toward Vero cells and human erythrocytes. CONCLUSION: The bactericidal and biofilm-killing activities of the new anti-YycG compounds were significantly better than the parent Compound 2.