Abstract
ObjectiveTo study the roles of AT1R, PLC-β1, CaM and other related signal molecules in the formation and development of hepatocellular carcinoma (HCC) and their correlation.MethodsELISA and immunohistochemistry were used to analyze the expressions of target proteins in serum and liver tissue of HCC patients, and the correlation between AT1R, PLC-β1 and CaM and postoperative survival status of patients was followed up and determined. CCK-8 method was used to screen the doses of Ang II and candesartan sensitive to HepG2 and HCCLM3 cells. Transwell experiment was used to observe the effects of different drugs on the migration and invasion activity of HCC cells. Meanwhile, flow cytometry and Western blot were used to detect the expression levels of AT1R, PLC-β1 and CaM in the cells. Then PLC-β1 siRNA was selected to transfect HCC cells, so as to further clarify the mechanism of the above signal proteins. HepG2 cells were inoculated under the hepatic capsule of mice to induce the formation of HCC in situ. Ang II and candesartan were used to stimulate HCC mice to observe the difference in liver appearance and measure the liver index. Finally, ELISA and immunofluorescence experiments were selected to analyze the levels of target proteins in mouse serum and liver tissue.ResultsThe expression levels of target proteins in serum and liver tissue of HCC patients were significantly increased, and the postoperative survival time of patients with high expression of AT1R, PLC-β1 or CaM was obviously shortened. Ang II and candesartan could significantly promote and inhibit the motility of HCC cells, and had different effects on the levels of AT1R, PLC-β1 and CaM in cells. However, in hepatocellular carcinoma cells transfected with PLC-β1 siRNA, the intervention ability of drugs was obviously weakened. Ang II could significantly promote the formation and progression of mouse HCC, while candesartan had the opposite effect. Meanwhile, medications could affect the expressions of target proteins in mouse serum and liver tissue.ConclusionAT1R, PLC-β1 and CaM may be risk factors affecting the formation and prognosis of HCC, and the PLC-β1/CaM signaling pathway mediated by AT1R is an important way to regulate the migration and invasion activity of HCC cells.
Highlights
Primary hepatocellular carcinoma (HCC) is one of the common malignant tumors in the digestive system
Further detection by IHC showed that the expressions of angiotensin II type 1 receptor (AT1R), Phospholipase C-β1 (PLC-β1) and CaM in HCC tissues were significantly higher than those in para-carcinoma tissues, and with the increase of Edmondson-Steiner pathological grade, the levels of the above-mentioned target proteins in HCC specimens increased to different degrees (Fig. 3D)
Kaplan–Meier survival curve was drawn, and it was found that the postoperative survival time of patients with high expression of AT1R, PLC-β1 or CaM was significantly shortened, which are the risk factors affecting the prognosis of HCC (Fig. 4A–C)
Summary
Primary hepatocellular carcinoma (HCC) is one of the common malignant tumors in the digestive system. The incidence rate of HCC presents an upward trend around the world. HCC exceeds 20/1,00,000, while the 5-year survival rate is only about 10%, making it the third largest malignant tumor in mortality, behind lung cancer and gastric cancer [1,2,3]. Due to its hidden onset and lack of early symptoms, most patients are already in the advanced stage of the disease when they are diagnosed, and even have advanced manifestations such as acute liver failure, HCC rupture and hemorrhage, and distant tumor metastasis [4]. Patients with poorly differentiated HCC have a significantly increased capacity for tumor cell invasion and angiogenesis in vivo, and a high recurrence rate after surgical treatment, leading to an obvious increase in mortality in these patients [5]. The exploration on related molecules such as AT1R, PLC-β1 and CaM can provide theoretical basis for finding novel drug targets
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
