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The gastrointestinal flora is composed of a large number of microorganisms with complex structure,which participates in the process of decomposition,digestion and absorption of nutrients,promotes the development of the body's immune system,inhibits the colonization of pathogenic bacteria,and affects the health and disease of the body.In recent years,with the advancement of sequencing technology,the relationship between gastrointestinal flora and gastrointestinal neoplasms has became a research hotspot.This article reviews the carcinogenic pathways of the gastrointestinal flora and the possible carcinogenic mechanisms of the gastrointestinal flora.
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Objective To study the effect of gambogic acid on apoptosis and autophagy in human hepatoma cells HepG2, and to detect its possible mechanism. Methods After exposure of HepG2 cells to gambogic acid at different concentration for 24 h, cell proliferation rates was determined by MTT assay, apoptosis rate was detected by the flow cytometry (FCM), formation of autophagic vacuoles was observed by the monodansyl cadaverine (MDC) fluorescence staining, expression level of apoptosis-related proteins Bax, bcl-2 and autophagy related protein Beclin 1 was detected by Western blot. Results HepG2 cell growth was inhibited by the gambogic acid dose dependence. After exposure to gambogic acid at 0, 2.0, 4.0 and 8.0 μmol/L for 24 h, cell apoptosis rate was significantly increased to 5.31 %, 29.18 %, 31.50 % and 46.09 %(P <0.05), MDC average fluorescence intensity was also significantly increased to 6.3 ±1.1, 82.6 ±4.5, 132.9±15.7 and 157.7±9.0 (P<0.01). Western blot showed that gambogic acid could promote the expression of apoptosis protein Bax (0.17 ±0.02, 0.75 ±0.06, 0.78 ±0.05, 0.89 ±0.10, P <0.05), and decrease the expression of anti-apoptosis protein bcl-2 (1.18 ±0.04, 0.90 ±0.06, 0.64 ±0.08, 0.57 ±0.05, P <0.05), meanwhile, it could also increase the expression of autophagy related protein Beclin (0.67±0.03, 0.92±0.04, 0.95±0.07, 1.04±0.06, P<0.05). Conclusion Gambogic acid can inhibit the growth of human hepatoma HepG2 cells by inducing apoptosis and autophagic cell death.
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Objective To investigate the expression of scaffold protein palladin in pancreatic ductal adenocarcinoma (PDAC) tissues and to discuss its clinicopathological significance.Methods 56 samples of PDAC and corresponding adjacent normal pancreas (NP) tissues were collected.Another 10 samples of chronic pancreatitis (CP) tissues were collected.Western blot analysis and immunohistochemistry assay were performed to detect the expression of protein palladin.The correlation of palladin expression with clinicopathological factors of PDAC was analyzed.Results Western blot analysis revealed that the expression of palladin in PDAC,CP and NP tissues were respectively 0.93±0.07,0.41±0.07 and 0.20±0.06,and the expression of palladin was significantly increased in PDAC tissues compared with NP and CP tissues (P ＜ 0.05),and its expression was significantly increased in CP tissues compared with NP tissues (P ＜ 0.05).Immunohistochemical staining showed that palladin was mainly expressed in activated myofibroblasts in PDAC tissues.The rate of palladin expression was 79 ％ (44/56),which was higher than that in NP tissues (2/10) and CP tissues (4/10),and its expression was found to be correlated with the degree of tumor differentiation,lymph node metastasis and clinical TNM classification (P ＜ 0.05),and it had no correlation with patient' s sex,age,tumor location and distant metastasis (P ＞ 0.05).Conclusions Scaffold protein palladin is highly expressed in PDAC tissues,and it is expressed in the activated myofibroblasts within tumor microenvironment.Scaffold protein palladin may be involved in the invasion and metastasis of PDAC.
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Objective To explore the influence of HepG2 cells' proliferation and autophagy by the Nrf2-ARE pathway,and provide the experimental basis for clinical exploring effective liver cancer treatment.Methods Hepatic carcinoma HepG2 cells were cultured,and its proliferation inhibition rates and the change of cell cycle' s in each phase were explored by the MTT assay and flow cytometry.The hepatoma cells' autophagy was qualitative observed by inverted phase contrast microscope and fluorescence microscope.Results Inhibitory rate of HepG2 cells was obviously higher in the Nrf2 inhibitor BML-111 group than control group (P ＜ 0.05),and the control group was aslo obviously higher than the Nrf2 inducer EGb group (P ＜ 0.05).Flow cytometric analysis showed that G1 phase cells in the cell cycle increased,S phase cells reduced and G2/M period cells relatively increased in the Nrf2 inhibitor BML-111 group.But G1 phase cells reduced,S phase cells increased and G2/M period cells relative reduced in the Nrf2 inducer EGb group.Inverted phase contrast microscope and fluorescence microscope checked that ranging from the size of the bubble and autophagosome formed in Hepatoma HepG2 cytoplasmic of the Nrf2 inhibitor BML-111 group.Conclusions The Nrf2-ARE pathway played an reverse inhibition on HepG2 cells' proliferation and autophagy.After the inhibition of Nrf2-ARE pathway,HepG2 cells mostly stayed in the G1 phase of the cell cycle.
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Objective To investigate the effect of ursodesoxycholic acid (UDCA) on JAK/STAT3/ COX-2 signal pathway in human hepatocellular carcinoma cells and the underlying mechanism of its antitumor effect.Methods In order to obtain the optimal concentration and time of UDCA,MTT assay was used to detect anti-proliferative activities of UDCA on SMMC-7721 cells induced by IL-6 in vitro.Cells were divided into control group,IL-6 group,AG490 (JAK2 inhibitor) group and UDCA group.The protein expressions of STAT3,p-STAT3 and COX-2 were measured by Western blot.Results MTT assay showed UDCA had obvious anti-proliferative activities on SMMC-7721 cells.The optimized concentrations were 50,100,200 μg/ml,the optimized culture time was 48 h.Western blot results showed that the expression of p-STAT3 and COX-2 were remarkably increased in IL-6 group than that in control group.There was no difference of STAT3 expression between the two groups.Compared with IL-6 group,the protein level of COX-2 was decreased in AG490 and UDCA groups,so was the expression of p-STAT3.But there was no change on STAT3 expression in AG490 and UDCA groups.Conclusion UDCA may decrease the proliferation of SMMC-7721 cells via inhibiting phosphorylation of STAT3 and down-regulating COX-2 exprcssion.
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Hepatic carcinoma is one of the most common malignant tumors in China.Autophagy activity and the change of Nrf2-ARE pathway play an important role in the process of liver tumors.Nrf2 which is an important regulator to liver cancer belongs to the CNC family.Research discovered that after the inhibition of autophagy,Nrf2-ARE pathway activation contributes to the progression of hepatocellular carcinoma.This article summarizes the relationship between autophagy and the Nrf2-ARE pathway and its impact on the hepatic carcinoma.
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The present study attempted to examine the effects of bile acid pool size on liver regeneration after hepatectomy. The rats were fed on 0.2% cholic acid (CA) or 2% cholestyramine for 7 days to induce a change in the bile acid size, and then a partial hepatectomy (PH) was performed. Rats fed on the normal diet served as the controls. Measurements were made on the rate of liver regeneration, the labeling indices of PCNA, the plasma total bile acids (TBA), and the mRNA expression of cholesterol 7alpha-hydroxylase (CYP7A1), farnesoid X receptor (FXR), and transcription factor c-Jun or c-fos. As compared with the normal and CA groups, the rate of liver regeneration was decreased on the day 3, and 7 after PH; the peak of the labeling indices of PCNA was delayed and the labeling indices were significantly reduced on the day 1; the TBA were also decreased on the day 1; the expression of FXR decreased but that of CYP7A1 increased at any given time; at the 1st, and 3rd h, the expression of c-Jun was declined in the cholestyramine group. The reduction in the bile acid pool size was found to delay the liver regeneration, which may be caused by the down-regulation of FXR and c-Jun expression.
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The liver regeneration is closely related to the bile acids. To avoid the toxic effects of bile acids on hepatocyte, the state of bile secretion, the rate-limiting enzyme of the bile acid synthesis, bile acids composition as well as the transporter changes at the process of liver regeneration. In vivo and in vitro experiments show that bile acids can promote liver cell proliferation, liver regeneration may be related to the signal which is released under the bile acid imbalance. The relationship between the liver regeneration and bile acid metabolism has an important practical significance in liver regeneration.
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Objective To investigate the effect of the lack of intestinal bile on liver regeneration after hepatectomy.Methods The model of interference with intestinal bile acid metabolism in rats was established by feeding rats with 0.2% cholic acid(cholic acid loading group), 2% cholestyramine resin(lack of bile group)and feeding the standard diet as the control group.Liver regeneration was compared among the 3 groups at 0, 1, 2, 3, and 7 d after 70% partial hepatectomy(PH)in rats and mRNA expression of the rate-limiting enzyme of bile acid biosynthesis(CYP7a1)and farnesoid X receptor (FXR)were detected.Results The rate of liver regeneration was significantly lower on days 3 and 7after PH in the lack of bile group than in the other groups(P＜0.05).On day 1, the labeling indices of PCNA and Ki-67 in the lack of bile group(22.21% ±2.31%、 17.25 % ± 6.50 %)were lower than those in the cholic acid loading group(44.4%±4.92%、 30.83% ± 3.91%)and control group (38.74% ±6.42% 、27.04% ±7.22%)and the peaking of labeling indices was delayed.After PH, the mRNA expression of FXR was significantly lower in the lack of bile group than in other groups.However, CYP7al mRNA had a trend towards increase after PH and was higher than that in other groups.Conclusion Lack of intestinal bile results in delayed liver regeneration of normal rat liver accompanied by decreased expression of FXR mRNA after hepatectomy.
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Regulation of liver regeneration is a complex pathophysiological process, accompanied by the participation of a large number of cytokines, such as the early stage of IL-6, TNF-α, the proliferation phase of HGF, TGFα, as well as the termination phase of TGFβl, and so on. These factors are coordinated in an orderly adjustment of liver cell proliferation. Enhancing the capacity of liver regeneration after liver resection and transplantation, study on molecular mechanism of liver regeneration is of great significance. This article summarizes liver regenerati after partial hepatectomy and the role of the relevant molecules.
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The Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily and has emerged as a key player in the control of multiple metabolic pathways. Bile acids are the major endogenous ligands for FXR, and by activating FXR have a variety of target genes, many of which are geared toward pre- venting synthesis and uptake and promoting excretion of bile acids. Here we summarized the latest results from studies on FXR target genes and functions in bile acids metabolism in this article.
