1.Study on the drug-resistant reversal effects of ginsenoside Rh2 in human hepatocellular carcinoma HepG2/ADM cells and its mechanism
Journal of Medical Postgraduates 2017;30(5):476-480
Objective Ginsenoside Rh2 can inhibit the proliferation of a variety of malignant tumor cells.However, little research has been done on the sensitivity of Rh2 in human hepatocellular carcinoma HepG2/ADM cells with multidrug resistance(MDR).This study aimed to explore the reversing effects of ginsenoside Rh2 on the MDR of human hepatocellular carcinoma HepG2/ADM cells and its potential mechanism.Methods MTT assay was applied to detect the effect of Rh2(0-250 μg/mL) on the viability of HepG2/ADM cells and screen out the optimum drug-resistant reversal concentration of Rh2.Cells were divided into 3 groups: HepG2/ADM group (without any medicine treatment), ADM group(ADM treatment for 48 h), ADM+40 μg/mL Rh2 group (pretreatment of 40μg/mL Rh2 for 30 min followed by ADM treatment for 48 h).Flow cytometry was applied to detect the effect of Rh2 on the fluorescence intensity of cellular Rh-123.RT-PCR was used to measure the expression of MDR1 gene.Western blot was used to detect the protein levels of P-gp, Bax, Bcl-2 and cleaved caspase-3.Results 40 μg/mL ginsenoside Rh2 significantly reversed the MDR of HepG2/ADM cells by a 2.55-to-3.70-fold increase in sensitivity.Furthermore, compared with ADM group, the efflux of Rh-123 in HepG2/ADM cells were remarkably inhibited by Rh2 in ADM+40 μg/mL Rh2 group (65.83±1.78 vs 78.21±1.26, P<0.01), along with the down-regulated expressions of MDR1 (0.48±0.02 vs 0.86±0.05, P<0.05), P-gp(0.97±0.04 vs 1.91±0.03,P<0.01), Bcl-2(1.25±0.05 vs 1.86±0.03, P<0.05) and the up-regulated protein level of Bax (1.76±0.04 vs 1.25±0.02,P<0.05) and cleved caspase-3(0.42±0.04 vs 38.26±5.45,P<0.05).Conclusion Ginsenoside Rh2 can effectively reverse the MDR of HepG2/ADM cells, and the potential mechanism is related to the decreased expressions of MDR1 and P-gp, the increasing drug concentration inside the cells and the Bax/Bcl-2 signaling pathway.
2.Over-expression of GSTP1 increases oxaliplatin-induced apoptosis in hu-man hepatoma HepG2 cells
Runtian LIU ; Congjing AN ; Yun BAI ; Jianxing ZHENG
Chinese Journal of Pathophysiology 2016;32(9):1579-1583
AIM: To investigate the effect of GSTP1 over-expression on the sensitivity of human hepatoma HepG2 cells to oxaliplatin (OXA).METHODS: Adenovirus carrying GSTP1 (Ad-GSTP1) was used to infect HepG2 cells for establishing the cell line over-expressing GSTP1.The cells were randomly divided into 6 groups: control, vehicle, Ad-GSTP1, OXA, OXA +vehicle and OXA +Ad-GSTP1.The cell survival rates were examined by CCK-8 assay, and the apoptotic rates were analyzed by flow cytometry.The protein levels of GSTP1, Akt, mTOR, p-Akt and p-mTOR were deter-mined by Western blot.RESULTS: OXA decreased the cell survival rate in a dose-dependent manner (P <0.05).The protein expression of GSTP1 increased after transfection with adenovirus.At basal level, up-regulation of GSTP1 signifi-cantly decreased the cell survival rate, increased the cell apoptosis, and inhibited the phosphorylation levels of Akt and mTOR (P <0.05).Moreover, GSTP1 over-expression enhanced the effect of OXA on the cell viability, cell apoptosis, and further inhibited the phosphorylation levels of Akt and mTOR ( P <0.05).CONCLUSION: Over-expression of GSTP1 augments the enhanced effect of OXA on HepG2 cell apoptosis, which may be related to the inactivation of Akt/mTOR signaling pathway.
3.Expression and clinical significance of X-box binding protein 1 in liver cancer
Haitao LU ; Sanguang LIU ; Jiansheng ZHANG ; Wenbin WANG ; Runtian LIU ; Changqing YAN ; Wei BIAN ; Shugui MA
Cancer Research and Clinic 2011;23(6):390-392
Objective To investigate the possible role of X-box binding protein (XBP1) expression at mRNA level in the hepatocarcinogenesis. Methods The expression of XBP1 at mRNA level was determined with RT-PCR method in liver carcinoma (42 cases), liver tissue adjacent to carcinoma (15 cases) and normal liver tissue (15 cases). XBP1 mRNA relative expression level was obtained by comparing with GAPDH mRNA level. The correlation between XBP1 expression and clinicopathological features of liver carcinoma were respectively analyzed. Results RT-PCR results showed that the expression of XBP1 mRNA in liver carcinoma cases (0.4396 ±0.0241) was significantly higher that that of liver tissues adjacent to carcinoma (0.4152±0.0252) and normal liver tissue (0.4095 ±0.0149), (F =12.79,P =0.001). No significant differences in the expression of XBP1 were found among different age and sex of the patients, different location, histological types, grade and metastatic status in liver carcinoma (P >0.05). Conclusion Increased expression of XBP1 mRNA is found in liver carcinoma but no correlation could be seen between XBP1 expression and clinicopathological features, which XBP1 is involved in the hepatocarcinogenesis.
4.Correlation between hypoglycemia and increased mortality of patients with acute decompensated liver cirrhosis
Runtian LIU ; Yun BAI ; Congjing AN ; Qiusheng LI ; Jianxing ZHENG ; Haiyan ZHANG
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2015;22(3):299-303
Objective To explore the correlation between hypoglycemia and the increased mortality of patients with acute decompensated liver cirrhosis.Methods A retrospective study was conducted on the clinical data of 120 patients with acute decompensated liver cirrhosis admitted to the Department of Hepatobiliary Surgery of the Second Hospital of Hebei Medical University from December 2011 to December 2014. The patients were divided into three groups: hypoglycemia group (glucose < 5.0 mmol/L, 21 cases), normoglycemia group (glucose 5.1 - 10.0 mmol/L, 84 cases), and hyperglycemia group (glucose > 10.0 mmol/L, 15 cases). The differences in hepatic carcinoma, decompensation symptoms, the incidence of known glycometabolic disorder, hospitalization situation, indicators of liver function and indexes of blood gas analysis were compared among three groups. The patients' age, hepatic carcinoma, ascites, hepatorenal syndrome, encephalopathy, bleeding, jaundice and glycometabolic disorder, etc were analyzed by the univariate analysis. The resulting risk factors with statistically significant differences were analyzed by multivariate logistic regression method in order to screen out the risk factors of increased mortality.Results The incidences of hepatorenal syndrome [42.9% (9/21) vs. 22.6% (19/84), 33.3% (5/15)] and jaundice [38.1% (7/21) vs. 20.2% (17/84), 13.3% (2/15)], rate of admission into intensive care unit (ICU) [14.3% (3/21) vs. 10.7% (9/84), 13.3% (2/15)] and in-hospital mortality [23.8% (5/21) vs. 10.7% (9/84), 20.0% (3/15)] in the hypoglycemia group were significantly higher than those in the normoglycemia group and hyperglycemia group (P < 0.05 orP < 0.01). The levels of aspartate-aminotransferase (AST), total bilirubin (TBil), serum creatinine (SCr) and international normalized ratio (INR) in hypoglycemia group were obviously higher than those in normoglycemia group and hyperglycemia group [AST (U/L): 628.412±78.625 vs. 170.167±87.035, 156.716±98.047; TBil (μmol/L): 154.122±34.201 vs. 86.712±48.905, 74.313±39.883; SCr (μmol/L): 160.243±56.341 vs. 107.211±59.692, 121.342±84.059; INR: 1.951±0.987 vs. 1.439±0.919, 1.423±0.653,P < 0.05 orP < 0.01]. The levels of HCO3- and base excess (BE) in hypoglycemia group were signicantly lower than those of normoglycemia group and hyperglycemia group [HCO3- (mmol/L): 18.154±10.937 vs. 23.135±11.119, 19.081±12.022; BE (mmol/L): -7.578±2.042 vs. -1.648±0.887, -5.402±2.005, allP < 0.01]. The pH value among three groups showed significant difference (7.352±2.878, 7.461±2.036, 7.219±2.017,P < 0.01). There were no statistically significant differences in alanine transaminase (ALT), blood ammonium, arterial partial pressure of oxygen (PaO2) and arterial partial pressure of carbon dioxide (PaCO2) and lactate among the three groups (all P > 0.05). Univariate analysis showed that advanced age, hepatic carcinoma, hepatorenal syndrome, bleeding, jaundice and glycometabolic disorder hypoglycemia were the risk factors of the death in patients with acute decompensated liver cirrhosis (P < 0.05 orP < 0.01). Multivariate logistic regression analysis showed that advanced age [odds ratio (OR) = 2.101, 95% confidence interval (95%CI) = 1.297 - 3.403,P = 0.000], hepatorenal syndrome (OR = 3.032, 95%CI = 1.462 - 6.286,P = 0.000) and hypoglycemia (OR = 3.267, 95%CI = 2.135 - 4.999,P = 0.031) were the independent risk factors of the patients' death.Conclusion Hypoglycemia has certain correlation to the increase of mortality in patients with acute decompensated liver cirrhosis.
5.Effects of shenmai injection on expression of TNF-alpha mRNA in peritoneal macrophages of scald mice.
Runtian WANG ; Chao GAO ; Dianwu LIU
Chinese Medical Journal 2002;115(2):293-295
OBJECTIVETo explore the effect of shenmai injection (SI) on expression of TNF-alpha mRNA in peritoneal macrophages (pMPhis) of scald mice.
METHODSBALB/c mice were inflicted with 11% of body surface area III degree scald and injected intraperitoneally (ip) with SI daily for 5 days, and expression of TNF-alpha mRNA in pMPhis was determined by semi-quantitative RT-PCR.
RESULTSIn scald mice, the expression of TNF-alpha mRNA in pMPhis increased significantly, but it was reduced obviously (P < 0.01) after SI administration, while the livability was increased markedly (P < 0.05).
CONCLUSIONSFor scald mice, the cause of death at early stage might be related to the high expression of TNF-alpha mRNA in pMPhis and the use of SI can decrease the death rate.
Animals ; Burns ; genetics ; mortality ; Drugs, Chinese Herbal ; pharmacology ; Gene Expression Regulation ; drug effects ; Macrophages, Peritoneal ; cytology ; drug effects ; metabolism ; Mice ; Mice, Inbred BALB C ; RNA, Messenger ; drug effects ; genetics ; metabolism ; Survival Rate ; Time Factors ; Tumor Necrosis Factor-alpha ; genetics
6.Laparoscopic pancreaticoduodenectomy: a report of 102 patients in one single center
Jiansheng ZHANG ; Tianyang WANG ; Jianhua LIU ; Dongrui LI ; Weihong ZHAO ; Pengxiang LIU ; Runtian LIU ; Shengxiong CHEN ; Xueqing LIU
Chinese Journal of Hepatobiliary Surgery 2020;26(3):199-202
Objective:To summarize the technical points of laparoscopic pancreaticoduodenectomy (LPD) carried out in a single center.Methods:The clinical data of 102 patients who underwent laparoscopic pancreaticoduodenectomy in 2018 at the Department of Hepatobiliary Surgery of the Second Hospital of Hebei Medical University were retrospectively analyzed, and the general conditions, operation time, intraoperative blood loss, and surgical operation were analyzed. Post-operative complications, hospital stay and other indicators were studied.Results:Of the 102 patients who were included, there were 57 males and 45 females, aged 15.0 to 79.0 (59.9±11.8) years old, with a body mass index (23.6±3.6) kg/m 2. For the 102 patients who underwent LPD, 6 were total pancreatic resection. Three were combined with vascular resection in the form of portal vein-superior mesentery vein segmental resection. The operation time was (376.6±87.2) min, the intraoperative blood loss was 350 (100, 800) ml, and the postoperative hospital stay was (17.0±5.9) days. Postoperative complications occurred in 26 of the 102 patients (25.5%), and more than two complications occurred in 17 patients. B/C grade pancreatic fistula occurred in 9 patients (9.4%), abdominal bleeding in 8 patients (7.8%), gastrointestinal bleeding in 2 patients (2.0%), biliary fistula in 4 patients (3.9%), and gastric emptying disorder in 5 patients (4.9%), 8 patients had pulmonary infection (7.8%). Five patients (4.9%) died during the perioperative period. Conclusion:The main technical points of LPD included en bloc resection, pancreaticojejunostomy, and vascular reconstruction. The basis of LPD is en bloc resection. Combined resection and reconstruction of vascular segments is a sign of maturity of LPD technology and a prerequisite for further development as a routine procedure.
7.Laparoscopic pancreaticoduodenectomy combined with major vascular resection and reconstruction:an analysis of 7 patients
Jiansheng ZHANG ; Qiusheng LI ; Jianhua LIU ; Dongrui LI ; Tianyang WANG ; Haibo WU ; Zhongqiang XING ; Runtian LIU ; Wenbin WANG ; Wenyan WEI ; Lu BIAN
Chinese Journal of Hepatobiliary Surgery 2017;23(10):674-679
Objective To review our experience in laparoscopic pancreaticoduodenectomy combined with major vascular resection and reconstruction.Methods Of 183 patients who underwent laparoscopic pancreaticoduodenectomy in our department from November 2013 to January 2017,major vascular resection and reconstruction using the SMA first approach for total mesopancreas excision was performed in 7 patients.The clinical data of these 7 patients were retrospectively analyzed.Results Total 3D laparoscopic surgery was performed in all these 7 patients.The mean operation time,mean blood loss and blood flow occlusion time were (551.4 ± 83.8) min,(671.3 ± 256.3) ml and (45.8 ± 6.7) min,respectively.Six out of 7 patients were pathologically diagnosed to have pancreatic adenocarcinoma with negative surgical margins.Two patients had lymphatic metastasis (the number of metastatic lymph node was 1 in each patient).The mean number of lymph nodes resected was (12.7 ± 5.8).The portal vein-superior mesenteric vein (PV-SMV) was segmentally resected and reconstructed using an end to end anastomosis following the preoperative plan in 4 patients.These included 2 patients who underwent total pancreatectomy.The portal vein was wedge-resected and reconstructed by venorrhaphy in 2 patients.The remaining 1 patient was histopathologically diagnosed to have a mass-type chronic pancreatitis.Only 1 patient was treated in the ICU for 1 day after surgery.Post-operative complications occurred in 2 patients and they were managed with nonsurgical treatment (PV-SMV thrombosis and gastric emptying disorder in 1 and a pancreatic leakage (level A) in 1).The mean length of post-operative hospital stay was (13.7 ± 3.2) days with no in-hospital mortality.Seven patients were alive by April 2017.The mean follow-up for the 6 patients with pancreatic adenocarcinoma was 4.5 (3.5 ~9) months.Conclusions Based on our experience in skillful and masterly major vascular resection and reconstruction in open surgery and on our experience in standard laparoscopic pancreaticoduodenectomy,laparoscopic pancreatieoduodenectomy combined with major vascular resection and reconstruction was feasible and safe.This surgery requires very mature skills in laparoscopic surgery.