| Background and Objection:Gastric cancer is one of the most common malignancies in the world.In China,the incidence and mortality of gastric cancer rank high in the tumor list.At present,the treatment of gastric cancer is mainly the surgical treatment for primary cases,and chemotherapy for advanced cases,because the early symptoms of gastric cancer are hidden and there is no nation-wide screening program for gastric cancer in China,so most patients have been diagnosed as advanced stage and have lost the indication for surgical treatment.Clinical studies have shown that the overall survival time of patients with advanced gastric cancer under different chemotherapy regimens has reached a plateau stage,with the median number ranging from 9 to 11 months.However,there are limited types of gastric cancer molecular target drugs that have passed the clinical trials and used in clinical therapies.It is not apparent that the combination of a molecular targeted drug and chemotherapy regimen does significantly improve the patients' overall survival time and quality of life,so there is a demand to explore new effective molecular targets.As a tumor-specific metabolic method,aerobic glycolysis,also known as the Warburg Effect,is widely presented in various types of tumors,and thus has the potential to become a new action target.Among the key enzymes in glycolysis,hexokinase 1(HK-I)and hexokinase 2(HK-II)have been found to be highly expressed in a variety of tumors.They not only increase the level of tumor glycolysis but also have nonenzymatic activities.For example,inhibiting apoptosis and regulating autophagy.Overall,HK-I and HK-II have a promoting effect on the malignant biology of cells and is considered as potential anti-tumor targets.The latest discovered hexokinase family member,hexokinase domain 1(HKDC1)also has a similar structure,so it is presumed to have similar functions,but there are few related studies,so this article will explore its relationship with gastric cancer.Purpose:1.To study the expression of HKDC1 in gastric cancer cells and its malignant biological effect on the gastric cancer cells;2.To study the correlation between the expression of HKDC1 in gastric cancer specimens and clinical characteristics.Method:1.Quantification of HKDC1 expression in gastric cancer and normal gastric epithelial cell lines by fluorescence quantitative PCR and Western blotting.2.Using small interfering RNA to knock down HKDC1 in a gastric cancer cell line that highly expresses HKDC1,and then explore the functional changes between negative control gastric cancer cells and HKDC1-knocked-down gastric cancer cells.3.Clinical specimens of 43 patients with gastric cancer were collected and immunohistochemically staining to be done to study the expression of HKDC1 in gastric cancer tissues.4.Using database to mine the clinical data of gastric cancer patients and analyze the relationship between the degree of HKDC1 expression and clinical characteristics.Result:1.Human normal gastric epithelial cells had extremely low expression of HKDC1 at both mRNA and protein levels,and HKDC1 were expressed in mRNA and protein to varying degrees in five different gastric cancer cell lines,with MKN-45 having the highest expression level.2.In cell experiments,siRNA was used to silence the expression of HKDC1 in MKN-45 cells.Compared with MKN-45 negative control group,the abilities of HKDC1-knocked-down MKN-45 cells such as cell proliferation,migration,invasion,and inhibition of apoptosis were significantly decreased(P<0.05).3.The expression of HKDC1 in the gastric cancer microarrays and clinically collected gastric cancer tissues was significantly higher than that in negative tissues(P<0.05).4.Clinical data analysis showed that there is no significant correlation between the expression of HKDC1 and the patients' age,gender and clinical stage(P>0.05),but HKDC1 high expression is correlated with higher differentiation grade(P<0.001).Conclusion:HKDC1 can promote the proliferation,migration and invasion abilities of gastric cancer cells and inhibit the apoptosis of gastric cancer cells.The expression of HKDC1 was significantly higher in gastric cancer tissues compared with negative tissues,and is related to the overall survival time and pathological grade. |
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