The NK1 receptor antagonist NKP608 inhibits proliferation of human colorectal cancer cells via Wnt signaling pathway

BACKGROUND: Neurokinin1 (NK1) receptor has played a vital role in the development of tumor. However, NKP608 as a NK1 receptor antagonist whether has the effect of the resistance of colorectal cancer is still unclear. Thereby, in this study, we investigated the role of NKP608 on human colorectal cancer and explored the underlying mechanism. METHODS: The cell proliferation of colorectal cancer cells was detected by cell counting kit-8 (CCK8) assay, cell migration and invasion were assessed by transwell assay, the apoptotic ratio of cells was assessed by Annexin V-fluorescein isothiocyanate/propidium iodide stained and flow cytometry. The involvement of molecular mechanisms was examined by western blot. RESULTS: In this study, we found that NKP608 inhibited the proliferation, migration/invasion of HCT116 cells. In addition, NKP608 reduced expressions of Wnt-3a, ß-catenin, Cyclin D1, and (vascular endothelial growth factor) VEGF while induced expression of E-Cadherin. Furthermore, flow cytometry analyzed that NKP608 induced apoptosis of HCT116 cells, consistently, western blotting detecting of apoptosis-related proteins revealed that NKP608 downregulated Bcl-2 while upregulated Bax and Active-Caspase-3. CONCLUSIONS: Taken together, our results demonstrated that NKP608 inhibited colorectal cancer cell proliferation, migration and invasion via suppressing the Wnt/ß-catenin signaling pathway. Therefore, NKP608 might represent a promising therapeutic agent in the treatment of colorectal cancer.

Skeletonized versus pedicled harvesting of bilateral internal mammary artery in coronary artery bypass graft: A case control study / 中国胸心血管外科临床杂志

@#Objective     To evaluate the safety and efficacy of skeletonized and pedicled harvesting of bilateral internal mammary artery (BIMA) in coronary artery bypass graft (CABG) surgery. Methods     From December 2015 to May 2017, 152 patients (128 males, 24 females, age of 56.5±6.8 years) underwent CABG using either skeletonized BIMA (s-BIMA group, n=73) or pedicled BIMA(p-BIMA group, n=79). The operative data and post-operative outcomes were analyzed in the s-BIMA group (61 males, 12 females, age of 56.6±7.0 years) and the p-BIMA group (67 males, 12 females, age of 56.3±6.7 years). Results     There was no peri-operative mortality. There was no statistical difference in operative time, cardiopulmonary bypass time, aortic cross-clamp time or internal mammary artery graft flow between the two groups. One patient(1.4%) in the s-BIMA group suffered from severe sternal wound complication, which was major sternal wound complication. Five patients (6.3%) in the p-BIMA group suffered from sternal wound complications, including 1(1.3%) with severe complication and 4(5.1%) with minor complication. One(1.4%) patient in the s-BIMA group and 7 (8.9%) patients in the p-BIMA group suffered from chylothorax. The chest tube drainage significantly reduced in the s-BIMA group, both in postoperative day 1(P=0.000) and postoperative day 1-3 (P=0.001). CT angiography showed no stenosis of BIMA in both groups. Conclusion     The use of skeletonized BIMA for CABG is safe and efficacious, with less sternal wound complications, chylothorax and chest tube drainage. Skeletonization should be   suggested if BIMA is harvested in CABG.