BACKGROUND Microwave ablation(MWA)is an effective treatment option for patients with primary liver cancer.However,it has been reported that the MWA procedure induces a hepatic inflammatory response and injury,which ma...BACKGROUND Microwave ablation(MWA)is an effective treatment option for patients with primary liver cancer.However,it has been reported that the MWA procedure induces a hepatic inflammatory response and injury,which may negatively affect the efficacy of MWA.As such,the discovery of reliable markers to monitor the patient’s response to MWA is needed.Golgi protein 73(GP73)has been shown to be associated with chronic liver disease.To date,the potential value of serum GP73 in the dynamic monitoring during MWA of liver cancer remains unclear.AIM To examine the effects of MWA on the serum levels of GP73 in patients with primary liver cancer.METHODS A total of 150 primary liver cancer patients with a single small lesion(≤3 cm in diameter)were retrospectively enrolled spanning the period between January 2016 and October 2018.All of the patients received MWA for the treatment of primary liver cancer.Serum GP73,alpha-fetoprotein(AFP),and widely used liver biochemical indicators[serum albumin,total bilirubin(TBIL),alanine aminotransferase(ALT),and aspartate aminotransferase(AST)]were compared before MWA and at different time points,including 1,2,and 4 wk following the ablation procedure.RESULTS Complete tumor ablation was achieved in 95.33%of the patients at 1 mo after MWA.The 1-,2-,and 3-year disease-free survival rates were 74.67%,59.33%,and 54.00%,respectively.The serum AFP levels were significantly decreased at 1,2,and 4 wk after MWA;they returned to the normal range at 12 wk after MWA;and they remained stable thereafter during follow-up in those cases without recurrence.In contrast,the serum GP73 levels were significantly increased at 1 and 2 wk after MWA.The serum GP73 levels reached the peak at 2 wk after MWA,started to decline after hepatoprotective treatment with glycyrrhizin and reduced glutathione,and returned to the pretreatment levels at 12 and 24 wk after MWA.Notably,the changes of serum GP73 in response to MWA were similar to those of TBIL,ALT,and AST.CONCLUSION Serum GP73 is markedly increased in response to MWA of liver cancer.Thus,serum GP73 holds potential as a marker to monitor MWA-induced inflammatory liver injury in need of amelioration.展开更多
BACKGROUND： Golgi protein 73 （GP73） is a promising bio- marker of hepatocellular carcinoma （HCC）. It decreases after surgical resection, and resumes upon recurrence, indicating a potential indicator for the effec...BACKGROUND： Golgi protein 73 （GP73） is a promising bio- marker of hepatocellular carcinoma （HCC）. It decreases after surgical resection, and resumes upon recurrence, indicating a potential indicator for the effectiveness of the treatment. But changes of GP73 after transcatheter arterial chemoemboliza- tion （TACE） have not been reported so far. This study was to investigate the dynamic changes of GP73 in HCC patients af- ter TACE treatment, and the possible underlying mechanisms in the cell cultures. METHODS： Blood samples were collected from 72 HCC pa- tients, before TACE, at day I and day 30 after TACE. GP73 lev- els were measured by Western blotting. The dynamic changes of GP73 were analyzed and compared with image changes and clinical data. The effects of chemotherapeutic agents （5-FU and pirarubicin） on GP73 expression were tested in three HCC cell lines （HepG2, HCCLM3 and MHCC97H）. RESULTS： The GP73 level was significantly elevated at day 1 and day 30 after TACE in HCC patients compared with that before the procedure （P〈0.05）. There was no statistical differ- ence between the two time points after TACE, nor correlationbetween GP73 levels and dinicopathological features, tumor metastasis, and patient survival. Pirarubicin, not 5-FU, signifi- cantly increased GP73 expression in three cell lines. CONCLUSIONS： Unlike surgical resection which decreases the GP73 level, TACE significantly increased GP73 expression in patients with HCC. No correlations were observed among GP73 levels, tumor characteristics and prognosis of patients with HCC.展开更多
Objective: The aim of the present study was to further evaluate the clinical value of single or joint of golgi protein 73 (GP73) and alphafetoprotein (AFP) in diagnosis of hepatocellular (HCC). Methods: One hundred an...Objective: The aim of the present study was to further evaluate the clinical value of single or joint of golgi protein 73 (GP73) and alphafetoprotein (AFP) in diagnosis of hepatocellular (HCC). Methods: One hundred and eighteen, 94 and 47 serum samples from the patients with HCC, chronic liver disease (CLD) and liver cirrhosis (LC) were collected, respectively. Serum levels of AFP and GP73 were assayed with commercial kit according to the manufacturer's instructions. Results: Patients with HCC had higher serum concentration of AFP than that of the patients with CLD (P < 0.01), but was similar to that of the patients with LC. Serum GP73 levels in the patients with CLD or LC were significantly lower than that in the patients from HCC group (P < 0.01). Among 118 HCC patients, the positive rate of GP73 and AFP was 80.5% and 48.3%, respectively (P < 0.001). The ROC curve analysis showed that the AUC value of GP73 was higher than that of serum AFP. Moreover, the sensitivity and the accuracy of GP73 were 77.1% and 82.6%, respectively, which were greater more than that of AFP at 90% specificity (28.8% and 59.8%, respectively). The AUC, the sensitivity and the accuracy of GP73 in combination of AFP (AFP/GP73) were 0.855, 78.0% and 83.0%, respectively, which were similar to that of GP73 alone but were much higher than that of the single marker AFP. Conclusion: For HCC diagnosing, GP73 was more sensitive and specific than AFP. The diagnostic value of AFP/GP73 was similar to GP73 but was much higher than AFP.展开更多
BACKGROUND Acute-on-chronic liver failure(ACLF)is the abrupt exacerbation of declined hepatic function in patients with chronic liver disease.AIM To explore the independent predictors of short-term prognosis in patien...BACKGROUND Acute-on-chronic liver failure(ACLF)is the abrupt exacerbation of declined hepatic function in patients with chronic liver disease.AIM To explore the independent predictors of short-term prognosis in patients with hepatitis B virus(HBV)-related ACLF and to establish a predictive short-term prognosis model for HBV-related ACLF.METHODS From January 2016 to December 2019,207 patients with HBV-related ACLF attending the 910^(th) Hospital of Chinese People's Liberation Army were continuously included in this retrospective study.Patients were stratified based on their survival status 3 mo after diagnosis.Information was collected regarding gender and age;coagulation function in terms of prothrombin time and international normalized ratio(INR);hematological profile in terms of neutrophil-tolymphocyte ratio(NLR)and platelet count(PLT);blood biochemistry in terms of alanine aminotransferase,aspartate aminotransferase,total bilirubin(Tbil),albumin,cholinesterase,blood urea nitrogen(BUN),creatinine,blood glucose,and sodium(Na);tumor markers including alpha-fetoprotein(AFP)and Golgi protein 73(GP73);virological indicators including HBV-DNA,HBsAg,HBeAg,Anti-HBe,and Anti-HBc;and complications including hepatic encephalopathy,hepatorenal syndrome,spontaneous peritonitis,gastrointestinal bleeding,and pulmonary infection.RESULTS There were 157 and 50 patients in the survival and death categories,respectively.Univariate analysis revealed significant differences in age,PLT,Tbil,BUN,NLR,HBsAg,AFP,GP73,INR,stage of liver failure,classification of liver failure,and incidence of complications(pulmonary infection,hepatic encephalopathy,spontaneous bacterial peritonitis,and upper gastrointestinal bleeding)between the two groups(P<0.05).GP73[hazard ratio(HR):1.009,95%confidence interval(CI):1.005-1.013,P=0.000],middle stage of liver failure(HR:5.056,95%CI:1.792-14.269,P=0.002),late stage of liver failure(HR:22.335,95%CI:8.544-58.388,P=0.000),pulmonary infection(HR:2.056,95%CI:1.145-3.690,P=0.016),hepatorenal syndrome(HR:6.847,95%CI:1.930-24.291,P=0.003),and HBsAg(HR:0.690,95%CI:0.524-0.908,P=0.008)were independent risk factors for short-term prognosis in patients with HBV-related ACLF.Following binary logistics regression analysis,we arrived at the following formula for predicting short-term prognosis:Logit(P)=Ln(P/1-P)=0.013×(GP73 ng/mL)+1.907×(middle stage of liver failure)+4.146×(late stage of liver failure)+0.734×(pulmonary infection)+22.320×(hepatorenal syndrome)-0.529×(HBsAg)-5.224.The predictive efficacy of the GP73-ACLF score was significantly better than that of the Model for End-Stage Liver Disease(MELD)and MELD-Na score models(P<0.05).CONCLUSION The stage of liver failure,presence of GP73,pulmonary infection,hepatorenal syndrome,and HBsAg are independent predictors of short-term prognosis in patients with HBV-related ACLF,and the GP73-ACLF model has good predictive value among these patients.展开更多
Hepatocellular carcinoma(HCC)is one of the most common malignant tumors with a low survival rate.The identification of mechanisms underlying the development of HCC helps uncover cellular and mo-lecular targets for the...Hepatocellular carcinoma(HCC)is one of the most common malignant tumors with a low survival rate.The identification of mechanisms underlying the development of HCC helps uncover cellular and mo-lecular targets for the diagnosis,prevention,and treatment of HCC.Golgi protein 73(GP73)level is up-regulated in HCC patients and potentially can be a therapeutic target.Despite many studies devoted to GP73 as a marker for HCC early diagnosis,there is little discussion about the function of GP73 in HCC tumorigenesis.Given the poor response to currently available HCC therapies,a better understanding of the role of GP73 in HCC may provide a new therapeutic target for HCC.The current paper summarizes the role of GP73 as a diagnostic marker as well as its roles in liver carcinogenesis.Its roles in other types of cancer are also discussed.展开更多
Background and Aims:As a hepatocellular carcinoma biomarker,serum Golgi protein 73(GP73)is reportedly related to inflammation.Acute-on-chronic liver failure(ACLF)is characterized by severe systemic inflammation.In thi...Background and Aims:As a hepatocellular carcinoma biomarker,serum Golgi protein 73(GP73)is reportedly related to inflammation.Acute-on-chronic liver failure(ACLF)is characterized by severe systemic inflammation.In this study,we aimed to explore the association between the GP73 level and short-term mortality in patients with alcohol-associated liver disease-related ACLF(ALD-ACLF).Methods:This retrospective cohort study involved 126 Chinese adults with ALD-ACLF.Baseline serum GP73 level was measured using enzymelinked immunosorbent assay.Patients were followed-up for 90 d and outcomes were assessed.Data were analyzed using multivariate Cox regression and piecewise linear regression analyses.The predictive value of GP73 and classic models for the short-term prognosis of participants were evaluated and compared using receiver operating characteristic curves.Results:The serum GP73 level was independently associated with an increased mortality risk in patients with ALD-ACLF.Compared with the lowest tertile,the highest serum GP73 level predisposed patients with ALD-ACLF to a higher mortality risk in the fully adjusted model[at 28 days:hazard ratio(HR):4.29(0.99–18.54),p=0.0511;at 90 days:HR:3.52(1.15–10.79),p=0.0276].Further analysis revealed a positive linear association.GP73 significantly improved the accuracy of the Child-Turcotte-Pugh score,model for end-stage liver disease score,and model for end-stage liver diseasesodium score in predicting short-time prognosis of patients with ALD-ACLF.Conclusions:The serum GP73 level is a significant predictor of the subsequent risk of death in patients with ALD-ACLF.GP73 improved the predictive value of classic prognostic scores.展开更多
Objective: To evaluate the inhibitory role of a novel oncolytic adenovirus(OA), GP73-SphK1 sR-Ad5, on the growth of hepatocellular carcinoma(HCC). Methods: GP73-SphK1 sR-Ad5 was constructed by integrating Golgi protei...Objective: To evaluate the inhibitory role of a novel oncolytic adenovirus(OA), GP73-SphK1 sR-Ad5, on the growth of hepatocellular carcinoma(HCC). Methods: GP73-SphK1 sR-Ad5 was constructed by integrating Golgi protein 73(GP73) promoter and sphingosine kinase 1(SphK1)-short hairpin RNA(shRNA) into adenovirus serotype 5(Ad5), and transfecting into HCC Huh7 cells and normal human liver HL-7702 cells. The expression of SphK1 and adenovirus early region 1(E1 A) was detected by quantitative real-time PCR(qRT-PCR) and western blot, respectively. Cell viability was detected by methylthiazolyldiphenyl-tetrazolium bromide(MTT) assay, and apoptotic rate was determined by flow cytometry. An Huh7 xenograft model was established in mice injected intratumorally with GP73-SphK 1 sR-Ad5. Twenty days after injection, the tumor volume and weight, and the survival time of the mice were recorded. The histopathological changes in tumor tissues were observed by hematoxylin-eosin(HE) staining and transmission electron microscopy(TEM). Results: Transfection of GP73-SphK1 sR-Ad5 significantly upregulated E1 A and downregulated SphK1 in Huh7 cells, but not in HL7702 cells. GP73-SphK1 sR-Ad5 transfection significantly decreased the viability and increased the apoptotic rate of Huh7 cells, but had no effect on HL7702 cells. Intratumoral injection of GP73-SphK1 sR-Ad5 into the Huh7 xenograft mouse model significantly decreased tumor volume and weight, and prolonged survival time. It also significantly decreased the tumor infiltration area and blood vessel density, and increased the percentages of cells with nucleus deformation and cells with condensed chromatin in tumor tissues. Conclusions: GP73-SphK1 sR-Ad5 serves as a novel OA and can inhibit HCC progression with high specificity and efficacy.展开更多
基金Supported by the Military Medical Science and Technology Committee of China,No.14MS095the Quanzhou Science and Technology Planning Project,No.2017Z018.
文摘BACKGROUND Microwave ablation(MWA)is an effective treatment option for patients with primary liver cancer.However,it has been reported that the MWA procedure induces a hepatic inflammatory response and injury,which may negatively affect the efficacy of MWA.As such,the discovery of reliable markers to monitor the patient’s response to MWA is needed.Golgi protein 73(GP73)has been shown to be associated with chronic liver disease.To date,the potential value of serum GP73 in the dynamic monitoring during MWA of liver cancer remains unclear.AIM To examine the effects of MWA on the serum levels of GP73 in patients with primary liver cancer.METHODS A total of 150 primary liver cancer patients with a single small lesion(≤3 cm in diameter)were retrospectively enrolled spanning the period between January 2016 and October 2018.All of the patients received MWA for the treatment of primary liver cancer.Serum GP73,alpha-fetoprotein(AFP),and widely used liver biochemical indicators[serum albumin,total bilirubin(TBIL),alanine aminotransferase(ALT),and aspartate aminotransferase(AST)]were compared before MWA and at different time points,including 1,2,and 4 wk following the ablation procedure.RESULTS Complete tumor ablation was achieved in 95.33%of the patients at 1 mo after MWA.The 1-,2-,and 3-year disease-free survival rates were 74.67%,59.33%,and 54.00%,respectively.The serum AFP levels were significantly decreased at 1,2,and 4 wk after MWA;they returned to the normal range at 12 wk after MWA;and they remained stable thereafter during follow-up in those cases without recurrence.In contrast,the serum GP73 levels were significantly increased at 1 and 2 wk after MWA.The serum GP73 levels reached the peak at 2 wk after MWA,started to decline after hepatoprotective treatment with glycyrrhizin and reduced glutathione,and returned to the pretreatment levels at 12 and 24 wk after MWA.Notably,the changes of serum GP73 in response to MWA were similar to those of TBIL,ALT,and AST.CONCLUSION Serum GP73 is markedly increased in response to MWA of liver cancer.Thus,serum GP73 holds potential as a marker to monitor MWA-induced inflammatory liver injury in need of amelioration.
基金supported by grants from the National Key Technology Research and Development Program of China 2012(BAI06B01)the National Natural Science Foundation of China(81201566)+1 种基金the Specialized Research Fund for the Doctoral Program of Higher Education(20121106110002)Wu Jieping Medical Foundation(LDWMF-SY-2011B002)
文摘BACKGROUND： Golgi protein 73 （GP73） is a promising bio- marker of hepatocellular carcinoma （HCC）. It decreases after surgical resection, and resumes upon recurrence, indicating a potential indicator for the effectiveness of the treatment. But changes of GP73 after transcatheter arterial chemoemboliza- tion （TACE） have not been reported so far. This study was to investigate the dynamic changes of GP73 in HCC patients af- ter TACE treatment, and the possible underlying mechanisms in the cell cultures. METHODS： Blood samples were collected from 72 HCC pa- tients, before TACE, at day I and day 30 after TACE. GP73 lev- els were measured by Western blotting. The dynamic changes of GP73 were analyzed and compared with image changes and clinical data. The effects of chemotherapeutic agents （5-FU and pirarubicin） on GP73 expression were tested in three HCC cell lines （HepG2, HCCLM3 and MHCC97H）. RESULTS： The GP73 level was significantly elevated at day 1 and day 30 after TACE in HCC patients compared with that before the procedure （P〈0.05）. There was no statistical differ- ence between the two time points after TACE, nor correlationbetween GP73 levels and dinicopathological features, tumor metastasis, and patient survival. Pirarubicin, not 5-FU, signifi- cantly increased GP73 expression in three cell lines. CONCLUSIONS： Unlike surgical resection which decreases the GP73 level, TACE significantly increased GP73 expression in patients with HCC. No correlations were observed among GP73 levels, tumor characteristics and prognosis of patients with HCC.
基金Supported by a grant from the International Collaboration Program from Nanjing Science and Technology Bureau (No. 201001139)
文摘Objective: The aim of the present study was to further evaluate the clinical value of single or joint of golgi protein 73 (GP73) and alphafetoprotein (AFP) in diagnosis of hepatocellular (HCC). Methods: One hundred and eighteen, 94 and 47 serum samples from the patients with HCC, chronic liver disease (CLD) and liver cirrhosis (LC) were collected, respectively. Serum levels of AFP and GP73 were assayed with commercial kit according to the manufacturer's instructions. Results: Patients with HCC had higher serum concentration of AFP than that of the patients with CLD (P < 0.01), but was similar to that of the patients with LC. Serum GP73 levels in the patients with CLD or LC were significantly lower than that in the patients from HCC group (P < 0.01). Among 118 HCC patients, the positive rate of GP73 and AFP was 80.5% and 48.3%, respectively (P < 0.001). The ROC curve analysis showed that the AUC value of GP73 was higher than that of serum AFP. Moreover, the sensitivity and the accuracy of GP73 were 77.1% and 82.6%, respectively, which were greater more than that of AFP at 90% specificity (28.8% and 59.8%, respectively). The AUC, the sensitivity and the accuracy of GP73 in combination of AFP (AFP/GP73) were 0.855, 78.0% and 83.0%, respectively, which were similar to that of GP73 alone but were much higher than that of the single marker AFP. Conclusion: For HCC diagnosing, GP73 was more sensitive and specific than AFP. The diagnostic value of AFP/GP73 was similar to GP73 but was much higher than AFP.
基金Supported by Science and Technology Project of Quanzhou to Dr.Zhengju Xu,No.2017Z018。
文摘BACKGROUND Acute-on-chronic liver failure(ACLF)is the abrupt exacerbation of declined hepatic function in patients with chronic liver disease.AIM To explore the independent predictors of short-term prognosis in patients with hepatitis B virus(HBV)-related ACLF and to establish a predictive short-term prognosis model for HBV-related ACLF.METHODS From January 2016 to December 2019,207 patients with HBV-related ACLF attending the 910^(th) Hospital of Chinese People's Liberation Army were continuously included in this retrospective study.Patients were stratified based on their survival status 3 mo after diagnosis.Information was collected regarding gender and age;coagulation function in terms of prothrombin time and international normalized ratio(INR);hematological profile in terms of neutrophil-tolymphocyte ratio(NLR)and platelet count(PLT);blood biochemistry in terms of alanine aminotransferase,aspartate aminotransferase,total bilirubin(Tbil),albumin,cholinesterase,blood urea nitrogen(BUN),creatinine,blood glucose,and sodium(Na);tumor markers including alpha-fetoprotein(AFP)and Golgi protein 73(GP73);virological indicators including HBV-DNA,HBsAg,HBeAg,Anti-HBe,and Anti-HBc;and complications including hepatic encephalopathy,hepatorenal syndrome,spontaneous peritonitis,gastrointestinal bleeding,and pulmonary infection.RESULTS There were 157 and 50 patients in the survival and death categories,respectively.Univariate analysis revealed significant differences in age,PLT,Tbil,BUN,NLR,HBsAg,AFP,GP73,INR,stage of liver failure,classification of liver failure,and incidence of complications(pulmonary infection,hepatic encephalopathy,spontaneous bacterial peritonitis,and upper gastrointestinal bleeding)between the two groups(P<0.05).GP73[hazard ratio(HR):1.009,95%confidence interval(CI):1.005-1.013,P=0.000],middle stage of liver failure(HR:5.056,95%CI:1.792-14.269,P=0.002),late stage of liver failure(HR:22.335,95%CI:8.544-58.388,P=0.000),pulmonary infection(HR:2.056,95%CI:1.145-3.690,P=0.016),hepatorenal syndrome(HR:6.847,95%CI:1.930-24.291,P=0.003),and HBsAg(HR:0.690,95%CI:0.524-0.908,P=0.008)were independent risk factors for short-term prognosis in patients with HBV-related ACLF.Following binary logistics regression analysis,we arrived at the following formula for predicting short-term prognosis:Logit(P)=Ln(P/1-P)=0.013×(GP73 ng/mL)+1.907×(middle stage of liver failure)+4.146×(late stage of liver failure)+0.734×(pulmonary infection)+22.320×(hepatorenal syndrome)-0.529×(HBsAg)-5.224.The predictive efficacy of the GP73-ACLF score was significantly better than that of the Model for End-Stage Liver Disease(MELD)and MELD-Na score models(P<0.05).CONCLUSION The stage of liver failure,presence of GP73,pulmonary infection,hepatorenal syndrome,and HBsAg are independent predictors of short-term prognosis in patients with HBV-related ACLF,and the GP73-ACLF model has good predictive value among these patients.
基金This study was supported bygrants funded by the USA National Institutes of Health(NIH)R01CA222490 to Y.-J.Y.Wanalong with grants from the National Natural Science Foundation of China Project number 81602456financial sup-port from the China Scholarship Council(CSC)to Y.Wang.
文摘Hepatocellular carcinoma(HCC)is one of the most common malignant tumors with a low survival rate.The identification of mechanisms underlying the development of HCC helps uncover cellular and mo-lecular targets for the diagnosis,prevention,and treatment of HCC.Golgi protein 73(GP73)level is up-regulated in HCC patients and potentially can be a therapeutic target.Despite many studies devoted to GP73 as a marker for HCC early diagnosis,there is little discussion about the function of GP73 in HCC tumorigenesis.Given the poor response to currently available HCC therapies,a better understanding of the role of GP73 in HCC may provide a new therapeutic target for HCC.The current paper summarizes the role of GP73 as a diagnostic marker as well as its roles in liver carcinogenesis.Its roles in other types of cancer are also discussed.
基金supported by a grant from the Capital’s Funds for Health Improvement and Research,China(NO.2020-1-5031).
文摘Background and Aims:As a hepatocellular carcinoma biomarker,serum Golgi protein 73(GP73)is reportedly related to inflammation.Acute-on-chronic liver failure(ACLF)is characterized by severe systemic inflammation.In this study,we aimed to explore the association between the GP73 level and short-term mortality in patients with alcohol-associated liver disease-related ACLF(ALD-ACLF).Methods:This retrospective cohort study involved 126 Chinese adults with ALD-ACLF.Baseline serum GP73 level was measured using enzymelinked immunosorbent assay.Patients were followed-up for 90 d and outcomes were assessed.Data were analyzed using multivariate Cox regression and piecewise linear regression analyses.The predictive value of GP73 and classic models for the short-term prognosis of participants were evaluated and compared using receiver operating characteristic curves.Results:The serum GP73 level was independently associated with an increased mortality risk in patients with ALD-ACLF.Compared with the lowest tertile,the highest serum GP73 level predisposed patients with ALD-ACLF to a higher mortality risk in the fully adjusted model[at 28 days:hazard ratio(HR):4.29(0.99–18.54),p=0.0511;at 90 days:HR:3.52(1.15–10.79),p=0.0276].Further analysis revealed a positive linear association.GP73 significantly improved the accuracy of the Child-Turcotte-Pugh score,model for end-stage liver disease score,and model for end-stage liver diseasesodium score in predicting short-time prognosis of patients with ALD-ACLF.Conclusions:The serum GP73 level is a significant predictor of the subsequent risk of death in patients with ALD-ACLF.GP73 improved the predictive value of classic prognostic scores.
基金Project supported by the Shandong Provincial Science and Technology Development Plan Project(No.2013GSF11853),China
文摘Objective: To evaluate the inhibitory role of a novel oncolytic adenovirus(OA), GP73-SphK1 sR-Ad5, on the growth of hepatocellular carcinoma(HCC). Methods: GP73-SphK1 sR-Ad5 was constructed by integrating Golgi protein 73(GP73) promoter and sphingosine kinase 1(SphK1)-short hairpin RNA(shRNA) into adenovirus serotype 5(Ad5), and transfecting into HCC Huh7 cells and normal human liver HL-7702 cells. The expression of SphK1 and adenovirus early region 1(E1 A) was detected by quantitative real-time PCR(qRT-PCR) and western blot, respectively. Cell viability was detected by methylthiazolyldiphenyl-tetrazolium bromide(MTT) assay, and apoptotic rate was determined by flow cytometry. An Huh7 xenograft model was established in mice injected intratumorally with GP73-SphK 1 sR-Ad5. Twenty days after injection, the tumor volume and weight, and the survival time of the mice were recorded. The histopathological changes in tumor tissues were observed by hematoxylin-eosin(HE) staining and transmission electron microscopy(TEM). Results: Transfection of GP73-SphK1 sR-Ad5 significantly upregulated E1 A and downregulated SphK1 in Huh7 cells, but not in HL7702 cells. GP73-SphK1 sR-Ad5 transfection significantly decreased the viability and increased the apoptotic rate of Huh7 cells, but had no effect on HL7702 cells. Intratumoral injection of GP73-SphK1 sR-Ad5 into the Huh7 xenograft mouse model significantly decreased tumor volume and weight, and prolonged survival time. It also significantly decreased the tumor infiltration area and blood vessel density, and increased the percentages of cells with nucleus deformation and cells with condensed chromatin in tumor tissues. Conclusions: GP73-SphK1 sR-Ad5 serves as a novel OA and can inhibit HCC progression with high specificity and efficacy.
