Molecular mechanisms of TUG1 in the proliferation, apoptosis, migration and invasion of cancer cells.

Long non-coding RNAs (lncRNAs) are RNA sequences >200 nucleotides in length that have no protein-coding capacity. lncRNAs serve key roles in multiple biological processes, such as tumorigenesis and tumor progression. Taurine upregulated 1 (TUG1) is a novel lncRNA that has been associated with human cancer. TUG1 has attracted increasing attention in recent years and has been documented to be abnormally expressed in different types of cancer. Numerous studies indicate that TUG1 may be significantly associated with tumor development and cell metabolism by regulating cell proliferation, invasion, metastasis, apoptosis, differentiation and drug resistance. TUG1 exerts its function via recruiting specific RNA-binding proteins, promoting target gene expression, influencing tumor angiogenesis and by functioning as a competing endogenous RNA (ceRNA). An increasing number of studies have demonstrated that ceRNAs serve a role in cancer development. TUG1 is considered to be a biomarker or a novel therapeutic target for the diagnosis and prognosis of different cancer types. The present review focuses on recent developments in the major underlying molecular mechanisms of TUG1 in cancer, including its role in cell proliferation, apoptosis, migration, invasion and drug resistance. Also discussed in the present review is the current knowledge regarding the regulation of TUG1.

Screening of immunosuppressive factors for biomarkers of breast cancer malignancy phenotypes and subtype-specific targeted therapy.

We aimed to screen and validate immunosuppressive factors in luminal- and basal-like breast cancer cell lines and tissue samples associated with malignant phenotypes. The mRNA microarray datasets, GSE40057 and GSE1561, were downloaded and remodeled, and differentially expressed genes were identified. Weighted gene co-expression network analysis (WGCNA) and gene ontology (GO) and KEGG pathway enrichment analysis were performed to explore the immune-related events related to the basal-like breast cancer. The online resources, GOBO, Kaplan-Meier Plotter and UALCAN, were employed to screen for immunosuppressive factors associated with breast cancer malignant phenotypes. Immunohistochemistry was used to evaluate VEGFA and MIF levels in breast tumors and normal breast tissues; qPCRs and western blots were used to validate the expression of clinical immuno-oncology (IO) therapeutic targets CD274 (PD-L1) and IL8 in cell lines. The results showed that various immune-related events contribute to basal-like breast cancer. First, TGFß1 and IL8 had higher average expression levels in more malignant cell lines; second, MIF and VEGFA had higher average expression levels in more malignant breast cancer tissues, and the high expression levels were associated with poor survival rate. Third, IO targets CD274 and IL8 which were confirmed to be more suitable for the treatment of basal-like breast cancer. In view of the above, during the formation and development of breast cancer, immune-related genes are always activated, and immunosuppressive factors, IL8, TGFß1, MIF, and VEGFA are up-regulated. Such molecules could be used as biomarkers for breast cancer prognosis. However, because individual immune-related factors can play several biological roles, the mechanistic relationship between immunosuppressive factors and breast cancer malignant phenotypes and the feasibility of their application as drug targets require further investigation.

Impact of Taurine on the proliferation and apoptosis of human cervical carcinoma cells and its mechanism.

BACKGROUND: Cervical cancer has the fourth highest incidence and mortality rate of all cancers in women worldwide; it seriously harms their physical and mental health. The aim of this study was to observe the roles and preliminary mechanism of Taurine (Tau)-induced apoptosis in cervical cancer cells. METHODS: Cells from the human cervical cancer cell line SiHa were transfected with the recombinant plasmid pEGFP-N1-MST1 (mammalian sterile 20-like kinase 1); then, the cell proliferation activity was analyzed by the MTT assay, cell apoptosis by flow cytometry, and the related protein levels by Western blotting. RESULTS: Tau inhibited the proliferation of SiHa cells and induced apoptosis in these cells (the apoptotic rate was 21.95% in the Tau 160 mmol/L group and 30% in the Tau 320 mmol/L group), upregulated the expression of the MST1 (control, 0.53; Tau 40-320 mmol/L groups, 0.84-1.45) and Bax (control, 0.45; Tau 40-320 mmol/L groups, 0.64-1.51) proteins (P < 0.01), and downregulated the expression of Bcl-2 (control, 1.28, Tau 40-320 mmol/L groups, 0.93-0.47) (P < 0.01). The overexpression of MST1 promoted the apoptosis of SiHa cells, enhanced the apoptosis-inductive effects of Tau (P < 0.01), upregulated the expression of the proapoptotic proteins p73, p53, PUMA (p53 upregulated modulator of apoptosis), and caspase-3, and promoted the phosphorylation of YAP (Yes-associated protein). CONCLUSIONS: Tau inhibited the proliferation and induced the apoptosis of cervical cancer SiHa cells. The MST1 protein plays an important role in the Tau-induced apoptosis of cervical cancer cells.

Taurine-upregulated gene 1 contributes to cancers through sponging microRNA.

Long non-coding RNAs (lncRNAs) are a class of RNAs whose transcripts are more than 200 nucleotides in length and lack protein-coding ability. Taurine-upregulated gene 1 (TUG1), a novel cancer-related lncRNA, has been documented to be abnormally expressed in various types of cancers and act as an oncogene or anti-oncogene. It has been considered previously that TUG1 is closely related to the cell proliferation, invasion, metastasis, and apoptosis of cancer. In recent years, it has been found that TUG1 acts as a microRNA (miRNA) sponge to indirectly regulate the expression of the miRNA target gene and dominates cancer progression in several types of cancers. However, TUG1 also binds to different miRNAs to produce diverse regulatory mechanisms in the same cancer. TUG1 is expected to be a biomarker and a new therapeutic target for the diagnosis and prognosis of certain cancers. In this review, we highlight the up-to-date original studies that focus on the role of TUG1 sponging miRNA in cancers and summarize the function of TUG1 in cancer progression. The novel TUG1-miRNA regulatory network is comprehensively and minutely included in this review. We hope that this review will help readers obtain a more detailed knowledge of the molecular mechanism by which TUG1 sponging miRNA plays its role in cancers, and provide some insights and directions for future cancer research.

Roles of the MST1-JNK signaling pathway in apoptosis of colorectal cancer cells induced by Taurine.

The aim of this study was to observe the impact of the mammalian sterile 20-like kinase 1-c-Jun N-terminal kinase (MST1-JNK) signaling pathway on apoptosis in colorectal cancer (CRC) cells induced by Taurine (Tau). Caco-2 and SW620 cells transfected with p-enhanced green fluorescent protein (EGFP)-MST1 or short interfering RNA (siRNA)-MST1 were treated with Tau for 48 h. Apoptosis was detected by flow cytometry, and the levels of MST1 and JNK were detected by western blotting. Compared with the control group, 80 mM Tau could significantly induce apoptosis of CRC cells, and the apoptotic rate increased with increasing Tau concentration (P < 0.01). Meanwhile, the protein levels of MST1 and phosphorylated (p)-JNK in Caco-2 cells increased significantly (P < 0.01). The apoptotic rate of the p-EGFP-MST1 plasmid-transfected cancer cells was significantly higher than that of the control group (P < 0.05); however, the apoptotic rate of the p-EGFP-MST1+Tau group was increased further (P < 0.01). Silencing the MST1 gene could decrease the apoptotic rate of cancer cells, and Tau treatment could reverse this decrease. Blocking the JNK signaling pathway significantly reduced the Tau-induced apoptotic rate of CRC cells. Thus, the MST1-JNK pathway plays an important role in Tau-induced apoptosis of CRC cells.

Effect of taurine on cell proliferation and apoptosis human lung cancer A549 cells.

To investigate the effects of taurine on cell proliferation and apoptosis, the human lung cancer A549 cell line and xenograft tumors in nude mice were used. The effects of taurine on cell proliferation and apoptosis were observed at time points of 24, 48 and 72 h after treatment using an MTT assay to detect the survival rate, and flow cytometry to detect the apoptotic rate. Western blot analysis was performed to examine the levels of p53 upregulated modulator of apoptosis (PUMA), BCL2, apoptosis regulator (Bcl-2) and BCL2-associated X, apoptosis regulator (Bax) in A549 cells. The level of PUMA, Bax and Bcl-2 proteins in the mouse xenograft tumors treated with taurine and/or exogenous PUMA were assessed by immunohistochemistry, with taurine suppressing the proliferation of the human lung cancer A549 cell line in a concentration-dependent manner, and it significantly enhanced the apoptosis rate at all concentrations. Taurine induced the significant upregulation of PUMA and Bax, but led to downregulation of Bcl-2. In comparison to the control group, taurine treatment markedly reduced the volume and weight of A549-derived xenograft tumors in nude mice. Expression of PUMA and Bax were upregulated in the xenograft tumors following taurine treatment, whereas Bcl-2 was downregulated. In addition, the inhibitory effect of taurine and exogenous PUMA on tumor growth was significantly higher than that of a single treatment of taurine or exogenous PUMA. It can therefore be concluded that taurine can inhibit cell proliferation of the human lung cancer A549 cell line and the growth of the xenograft tumors, whereas PUMA serves an important role in taurine-induced growth suppression.

New Insights into the Role of Endoplasmic Reticulum Stress in Breast Cancer Metastasis.

Cellular stress severely disrupts endoplasmic reticulum (ER) function, leading to the abnormal accumulation of unfolded or misfolded proteins in the ER and subsequent development of endoplasmic reticulum stress (ERS). To accommodate the occurrence of ERS, cells have evolved a highly conserved, self-protecting signal transduction pathway called the unfolded protein response. Notably, ERS signaling is involved in the development of a variety of diseases and is closely related to tumor development, particularly in breast cancer. This review discusses recent research regarding associations between ERS and tumor metastasis. The information presented here will help researchers elucidate the precise mechanisms underlying ERS-mediated tumor metastasis and provide new directions for tumor therapies.

Inhibitory effect and mechanism of exogenous mammalian sterile 20-like kinase 1 on the growth of human colorectal cancer.

The present study aimed to observe the inhibitory effect and preliminary mechanism of exogenous mammalian sterile 20-like kinase 1 (MST1) on the growth of colorectal cancer SW480 cells. The SW480 cells were randomly divided into the following groups: Control, empty enhanced green fluorescent protein (EGFP) plasmid (pEGFP-N1), MST1 EGFP plasmid (pEGFP-MST1), 20 µmol/l fluorouracil (5-FU) and pEGFP-MST1 + 5-FU. An MTS colorimetric assay was used to detect cell viability, Hoechst 33342 staining was used to observe cell apoptosis, and western blotting and immunohistochemistry were used to detect the levels of the proteins MST1, yes-associated protein (YAP), phospho-YAP1 (Ser127), p53 and p53 upregulated modulator of apoptosis (PUMA). In addition, nude mice were injected with SW480 cells to assess the tumor inhibition rates. Compared with the control group, the growth inhibition and apoptosis rates, the levels of MST1, p53 and PUMA, and the ratios of phospho-YAP1/YAP in the pEGFP-MST1 and pEGFP-MST1 + 5-FU groups were increased significantly (P<0.01). Additionally, relative to the control group, the tumor inhibition rates in the nude mice transplanted with SW480 cells of the pEGFP-MST1 and pEGFP-MST1 + 5-FU groups were 48.52±1.63 and 87.28±2.58%, respectively, and the positive rates of phospho-YAP1 (Ser127) protein in nuclei increased significantly (P<0.01). Overall, exogenous MST1 effectively inhibited the proliferation and growth of transplanted human colorectal cancer cells and promoted cancer cell apoptosis. The mechanism involved may be associated with the increase of intracellular phospho-YAP1 (Ser127) protein.

Effect of taurine on the proliferation and apoptosis of human hepatocellular carcinoma HepG2 cells.

The aim of the present study was to observe the effect and molecular mechanism of taurine (Tau) on the cell proliferation and apoptosis of human hepatocellular carcinoma (HHCC) HepG2 cells. HHCC HepG2 cells were used as target cells, and the cell survival rate was assessed using a multi-time-step method. The p53 upregulated modulator of apoptosis (PUMA) gene was transiently transfected by lipofection and subsequently silenced with specific small interfering (si)RNA. The cell apoptosis rate was detected by flow cytometry, and protein expression levels were analyzed with western blotting. Addition of 20-160 mM Tau was shown to have a significant inhibitory effect on cell proliferation, while promoting the induction of HHCC HepG2 cell apoptosis (P<0.05). Transfection of the PUMA gene significantly enhanced the ability of Tau to inhibit proliferation and induce apoptosis of HepG2 cells. In addition, transfection of the PUMA gene increased the protein expression of B-cell lymphoma-2-associated X and reduced the expression of B-cell lymphoma-2 (P<0.05). Silencing the PUMA gene with specific siRNA was demonstrated to significantly reduce the ability of Tau to inhibit proliferation and induce the apoptosis of HHCC HepG2 cells (P<0.01). Therefore, the PUMA gene was shown to have an important role in mechanism underlying the effect that Tau exerts on cell proliferation and apoptosis in HHCC HepG2 cells.

Exogenous p53 upregulated modulator of apoptosis (PUMA) decreases growth of lung cancer A549 cells.

PURPOSE: To investigate the influence of exogenous p53 upregulated modulator of apoptosis (PUMA) expression on cell proliferation and apoptosis in human non-small cell lung cancer A549 cells and transplanted tumor cell growth in nude mice. MATERIALS AND METHODS: A549 cells were divided into the following groups: control, non- carrier (NC), PUMA (transfected with pCEP4- (HA) 2-PUMA plasmid), DDP (10 µg/mL cisplatin treatment) and PUMA+DDP (transfected with pCEP4-(HA)2-PUMA plasmid and 10 µg/mL cisplatin treatment). The MTT method was used to detect the cell survival rate. Cell apoptosis rates were measured by flow cytometry, and PUMA, Bax and Bcl-2 protein expression levels were measured by Western blotting. RESULTS: Compared to the control group, the PUMA, DDP and PUMA+DDP groups all had significantly decreased A549 cell proliferation (p<0.01), with the largest reduction in the PUMA+DDP group. Conversely, the apoptosis rates of the three groups were significantly increased (P<0.01), and the PUMA and DDP treatments were synergistic. Moreover, Bax protein levels significantly increased (p<0.01), while Bcl-2 protein levels significantly decreased (p<0.01). Finally, both the volume and the weights of transplanted tumors were significantly reduced (p<0.01), and the inhibition ratio of the PUMA+DDP group was significantly higher than in the single DDP or PUMA groups. CONCLUSIONS: Exogenous PUMA effectively inhibited lung cancer A549 cell proliferation and transplanted tumor growth by increasing Bax protein levels and reducing Bcl-2 protein levels.

Taurine induces the apoptosis of breast cancer cells by regulating apoptosis-related proteins of mitochondria.

Taurine (Tau), the most abundant free amino acid in humans has numerous potential health benefits through its antioxidant and anti-inflammatory properties. However, limited studies have assessed its effect on tumors and the antitumor mechanism remains unknown. The present study investigated the cellular and molecular changes induced by Tau, leading to the induction of apoptosis in human breast cancer cell lines MCF-7 and MDA-MB-231. MCF-7 is p53 proficient (p53+/+) and MDA-MB-231 is a p53 null mutant (p53-/-). Cell proliferation and viability were assessed by MTT. Flow cytometry and hoechst33342 fluorescent staining were employed to detect apoptosis. Spectrophotometry was used to detect caspase-3 activity. Reverse transcription-polymerase chain reaction and western blot analysis were used to detect the levels of mRNA and proteins of p53-upregulated modulator of apoptosis (PUMA), Bax and Bcl-2. Finally, the affect of Tau on the growth of MDA-MB-231-cell-nude mice xenografts was examined. In the study, Tau inhibited growth and induced apoptosis of the two cell lines in a concentration- and time-dependent manner. Notably, the inhibitory effect of Tau on p53-/- cancer cells was clearly significant compared to the p53+/+ cancer cells. Further studies showed that Tau promoted apoptosis in human breast cancer cells and inhibited the growth of tumor in nude mice by inducing the expression of PUMA, which further up- and downregulated the expression of Bax and Bcl-2 protein, giving rise to increased activation of caspase-3. Collectively, these results indicate that Tau is a potent candidate for the chemotherapy of breast cancer through increasing the PUMA expression independent of p53 status.

MicroRNA-206 overexpression promotes apoptosis, induces cell cycle arrest and inhibits the migration of human hepatocellular carcinoma HepG2 cells.

MicroRNA-206 (miR-206) is known to regulate cell proliferation and migration and is involved in various types of cancer. However, the role of miR-206 in human hepatocellular carcinoma (HHC) has not been previously reported. In the present study, the expression of Notch3 in HCC and adjacent non-neoplastic tissue was immunohistochemically assessed on formalin-fixed, paraffin-embedded sections. miR-206 mimics were transiently transfected into HepG2 cells using Lipofectamine™ 2000. Subsequently, we evaluated the role of miR-206 in cell proliferation, apoptosis, cell cycle arrest and migration by MTS assay, Hoechst 33342 staining, Annexin V-FITC/PI assay, flow cytometry and wound healing assay. Using quantitative reverse transcription polymerase chain reaction (qRT­PCR) and western blot analysis, we detected the expression of Notch3, Bax, Bcl-2, Hes1, p57 and matrix metalloproteinase (MMP)-9 at the mRNA and protein level, respectively. In addition, we measured the expression of miR-206 at the mRNA level and that of caspase-3 at the protein level. After miR-206 was upregulated in HepG2 cells, Notch3, Hes1, Bcl-2 and MMP-9 were downregulated both at the mRNA and protein level, whereas p57 and Bax were upregulated. Cleaved caspase-3 protein expression was also markedly increased. Cell proliferation was significantly attenuated and apoptosis was markedly increased. Furthermore, miR-206 overexpression induced cell cycle arrest and inhibited the migration of HepG2 cells. Taken together, our results uggest that miR-206 is a potential regulator of apoptosis, the cell cycle and migration in HepG2 cells and that it has the potential for use in the targeted therapy of HCC and is a novel tumor suppressor.

Mechanism of taurine-induced apoptosis in human colon cancer cells.

Taurine (Tau) has been shown to possess cancer therapeutic effect through induction of apoptosis, while the underlying molecular mechanism of its anti-cancer effect is not well understood. PUMA (p53-upregulated modulator of apoptosis) plays an important role in the process of apoptosis induction in a variety of human tumor cells in both p53-dependent and -independent manners. However, whether PUMA is involved in the process of Tau-induced apoptosis in cancer cells has not been well studied. In the present study, we treated human colorectal cancer cells HT-29 (mutant p53) and LoVo (wild-type p53) with different concentrations of Tau, which led to the repression of cell proliferation and induction of apoptosis in both cell lines. Meanwhile, we also observed the increased expression of PUMA and high Bax/Bcl-2 ratios. To determine the role of PUMA in Tau-induced apoptosis, we used small interfering RNA interference to suppress PUMA expression. As a result, apoptosis was decreased in response to Tau treatment. All these results indicated that PUMA plays a critical role in Tau-induced apoptosis pathway in human colorectal cancer cells. Demonstration of the molecular mechanism involved in the anti-tumor effect of Tau may be useful in the therapeutic target selection for p53-deficient colorectal cancer.

Effect of Mst1 overexpression on the growth of human hepatocellular carcinoma HepG2 cells and the sensitivity to cisplatin in vitro.

Mammalian STE20-like kinase 1 (Mst1) is the mammalian homologue of Drosophila Hippo, a major inhibitor of cell proliferation in Drosophila. It ubiquitously encodes serine threonine kinase that belongs to the family of protein kinases related to yeast STE20, and is involved in cell proliferation, apoptosis, oncogenesis, and organ growth. Recent studies have shown that Mst1 has tumor-suppressor function, and the deletion or mutation of Mst1 is reported to be associated with tumorigenesis. To investigate the effect of overexpression of Mst1 on the growth of human liver cancer cell line HepG2 cells and the sensitivity to cisplatin in vitro, here we constructed recombinant eukaryotic expression vector pEGFP-N1-Mst1 containing Mst1 gene, and transiently transfected into HepG2 cells. The effects of Mst1 overexpression on the cell proliferation and apoptosis, the phosphorylation status of Yes-associated protein, and the mRNA transcript levels of connective tissue growth factor (CTGF), amphiregulin (AREG), and birc5 (Survivin) were determined. Results showed that overexpression of Mst1 inhibited cell proliferation, induced apoptosis of HepG2 cells, promoted YAP (Ser127) phosphorylation, and downregulated the mRNA expression of CTGF, AREG, and Survivin. We also investigated the relationship between the expression and cleavage of Mst1 and cisplatin-induced cell death. We found that Mst1 overexpression could induce cisplatin chemosensitivity, and cisplatin could promote the cleavage of Mst1 without affecting the expression of Mst1. Overall, our results indicated that Mst1 might be a promising anticancer target.

Effect of diallyl trisulfide on human ovarian cancer SKOV- 3/DDP cell apoptosis.

AIM: To investigate the effects of diallyl trisulfide (DT) on apoptosis of cisplatin (DDP)-resistant human epithelial ovarian cancer SKOV-3 cells (SKOV-3/DDP), and the role of p53 upregulated modulator of apoptosis (PUMA). METHODS: SKOV-3/DDP cells were randomly divided into control, DT, DPP and DPP+DT groups, which were treated with DT or combined DT and DDP. All cells were incubated for 48 h. and apoptosis rates were assessed by flow cytometry. mRNA and protein expression of PUMA, Bax and Bcl-2 was determined by RT-PCR and Western blot assays, respectively. RESULTS: Compared with control group, the apoptosis rates of SKOV-3/DDP cells in DT groups were obviously increased, with dose-dependence (P < 0.05), the mRNA and protein expressions of PUMA, Bax also being up-regulated (P < 0.05), while those of Bcl-2 were down-regulated (P < 0.05). Compared with DT groups, the apoptosis rate in the DDP+DT group was significantly increased (P < 0.05). After knockdown of PUMA with specific siRNA, the apoptosis rate of SKOV-3/DDP cells was obviously decreased (P < 0.05). CONCLUSION: DT can promote the apoptosis of SKOV-3/DDP cells with PUMA playing a critical role.

Inhibitory effect of p53 upregulated modulator of apoptosis targeting siRNA on hypoxia/reoxygenation-induced cardiomyocyte apoptosis in rats.

OBJECTIVES: The effect of p53 upregulated modulator of apoptosis (PUMA) in hypoxia/reoxygenation-induced cardiomyocyte injuries in rats was investigated. METHODS: PUMA-targeting (si-PUMA) and scramble siRNAs were designed and transfected into primarily rat cardiomyocytes in vitro. RESULTS: RT-PCR and Western blot analysis showed that 50 nmol/l of si-PUMA can specifically inhibit PUMA expression. MTT assay and lactate dehydrogenase activity detection showed that the cell survival rate in the si-PUMA group was enhanced and that the lactate dehydrogenase enzymatic activity dramatically decreased compared with the control group (p < 0.01). Spectrophotometry, as well as annexin V and propidium iodide staining, combined with flow cytometry, revealed that caspase-3 activity in the si-PUMA group was downregulated and the apoptotic rate was decreased (p < 0.01). RT-PCR also showed that Bax expression was downregulated and Bcl-2 expression was upregulated in the si-PUMA group, compared with the control group (p < 0.05). si-PUMA protects cardiomyocytes from apoptosis. CONCLUSION: PUMA mediates hypoxia/reoxygenation-induced cardiomyocyte apoptosis, which can be a potential target of gene therapy for ischemia/reperfusion cardiomyocyte injuries.

[Hippo signaling pathway in mammals: a new therapeutic target for tumors].

Hippo signaling pathway was first discovered in Drosophila as regulator of cell proliferation and apoptosis during development. It has been widely reported that Hippo signaling pathway plays an essential role in embryonic differentiation, pattern formation and adult cell homeostasis. Furthermore, Hippo signaling has close correlation with Wnt and Notch signaling pathways, and has an important effect on tumor initiation and progression. Recent studies have shown that the Drosophila Hippo signaling pathway is highly conserved over evolutionary time, the mammalian Hippo signaling pathway has been implicated in regulating cell contact inhibition, organsize and tumorigenesis. This review firstly focuses on the composition, regulatory mechanism and physiological functions of mammalian Hippo signaling pathway, and then lists the relationship with other signaling pathways and protein factors, and tumors in mammals. Finally, the therapeutic approaches to targeting Hippo signaling pathway components or regulators have also been summarized, which might be beneficial to tumor therapeutic intervention.

Protective effect of glucose-insulin-potassium (GIK) on intestinal tissues after severe burn in experimental rats.

Intestinal barrier damage after scald and burns, other trauma or major operations result in severe intestinal infections that cause serious consequences. Therefore, it is important to develop methods to protect intestinal barrier after severe burns. This study used rats that had full-thickness burn of approximately 30% of the total body surface area to investigate the effect and mechanism of glucose-insulin-potassium (GIK) and provide experimental evidence for application of GIK in protecting the intestine after burns or other trauma and major surgeries. The results show that the degree of intestinal damage and plasma diamine oxidase (DAO) levels in GIK (the concentrations of glucose, insulin, sodium chloride and potassium chloride were 100 g l(-1), 70 U l(-1), 9 g l(-1) and 5 g l(-1), respectively) and insulin (30 IU l(-1)) treatment groups were significantly lower than that in control group; the status of anti-inflammatory and pro-inflammatory cytokines and the ratio between them in GIK and insulin groups also significantly improved compared to those in control group; intestinal tumour necrosis factor-alpha (TNFα), nuclear factor-kappaB (NF-κB) and interleukin-10 (IL-10) messenger RNA (mRNA) expression and IL10/TNFα in GIK and insulin groups 2 days after the injury were also improved significantly compared to those in control group. All the indices including body weight detected in GIK group were improved to those in insulin group. Taken together, these results show that GIK and insulin show protective effect on intestine after severe burn, which may relate to controlling hyperglycaemia and regulating intestinal expression of NFκB and pro-inflammatory and anti-inflammatory cytokine genes by GIK and insulin; the protective effect of GIK on intestinal tissue after severe burn is superior to that of using insulin alone, which may attribute to improving the nutritional status by glucose supplement and the relatively higher dose of insulin in the GIK group.

[Study on apoptosis of human stomach SGC-7901 cells induced by extracts of Solanum lyratum].

OBJECTIVE: To investigate the effects of extracts of Solanum lyratum (ESL) on the apoptosis of Human stomach cancer SGC-7901 cells. METHODS: Dried whole herbs of Solanum lyratum were extracted by boiling distilled water. SGC-7901 cells were randomly divided into control group, ESL-treated groups (12.5 g/L, 25 g/L, 50 g/L) and the positive control (25 mg/L DDP) group. The growth inhibitory rate was evaluated by MTT assay. Morphological changes of apoptosis were observed with fluorescence microscope. Cell apoptosis rate was determined by flow cytometry. Expressions of bcl-xl, Caspase-9 and bid mRNA were detected by semi-quantitive RT-PCR. The activity of Caspase-3 was detected by Fluorospectrophotometry. RESULTS: Compared with control group, the cell proliferation inhibitory rate and apoptosis rate of human stomach cancer SGC-7901 cells increased obviously (P < 0.05). There were obvious changes of morphology of the SGC-7901 cells as the nuclear shrinkage, chromatin condensation and margination; The expression of bcl-xl mRNA decreased obviously (P < 0.05), the expression of Caspase-9 and bid mRNA increased obviously respectively (P < 0.05), and displayed effect in a dose-dependent manner in the SGC-7901 cells of the ESL-treated groups. The activity of Caspase-3 in the SGC-7901 cells of the ESL-treated groups were higher than that of the control group significantly (P < 0.01). CONCLUSION: ESL can induce apoptosis and inhibit proliferation of the human stomach cancer SGC-7901 cells by regulating expression of bcl-xl, Caspase-9 and bid genes and strengthening the activity of Caspase-3.