Marsdeniae tenacissimae extract (MTE) suppresses cell proliferation by attenuating VEGF/VEGFR2 interactions and promotes apoptosis through regulating PKC pathway in human umbilical vein endothelial cells / 中国天然药物

Marsdeniae tenacissimae extract (MTE), commonly known as Xiao-Ai-Ping in China, is a traditional Chinese herb medicine capable of inhibiting proliferation and metastasis and boosting apoptosis in various cancer cells. However, little is known about the contribution of MTE towards tumor angiogenesis and the underlying mechanism. The present study aimed to evaluate the effects of MTE on the proliferation and apoptosis of human umbilical vein endothelial cells (HUVECs) and the molecular mechanism. 3-(4,5-dimethylthiazol-2-yl)-5(3-carboxymethoxyphenyl)-2-(4-sulfopheny)-2H-tetrazolium, inner salt (MTS) and PI-stained flow cytometry assays revealed that MTE dose-dependently reduced the proliferation of HUVECs by arresting cell cycle at S phase (P < 0.05). Annexin V-FITC/PI-stained flow cytometry confirmed that MTE (160 μL·L) enhanced the apoptosis of HUVECs significantly (P < 0.001). Real-time quantitative RT-PCR and Western blot analyses showed an increase in Bax expression and a sharply decline in Bcl-2 expression; caspase-3 was activated simultaneously in a dose-dependent manner (P < 0.05). Further study observed the dose-dependent down-regulation of vascular endothelial growth factor (VEGF) receptor-2 (VEGFR-2), P2Y6 receptor (P2Y6R), and chemokine (C-C motif) ligand 2 (CCL-2), along with the activation of PKC Δ and up-regulation of p53 in a dose-dependent manner in MTE-treated selected cells (P < 0.05). Collectively, the results from the present study suggested that MTE suppressed the proliferation by attenuating CCL-2-mediated VEGF/VEGFR2 interactions and promoted the apoptosis through PKCΔ-induced p53-dependent mitochondrial pathway in HUVECs, supporting that MTE may be developed as a potent anti-cancer medicine.

Proliferative and apoptotic effects of andrographolide on the BGC-823 human gastric cancer cell line / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Andrographolide has been shown to have anticancer activity on diverse cancer cell lines representing different types of human cancers. The aim of this research was to investigate the anticancer and apoptotic effects of andrographolide on the BGC-823 human gastric cancer cell line.</p><p><b>METHODS</b>Cell proliferation and IC50 were evaluated using MTT assay, cell-cycle analysis with flow cytometry apoptotic effects with Annexin-V/propidium iodide double-staining assay, and morphologic structure with transmission electron microscopy. Immunohistochemistry and reverse-transcription PCR was used to analyze Bcl-2, Bax, and caspase-3 expressions.</p><p><b>RESULTS</b>Andrographolide showed a time- and concentration-dependent inhibitory effects on BGC-823 cell growth. Compared to controls, the number of cells in the G0-G1-phase increased significantly, S and G2-M-phase cells decreased after 48 hours of treatment with andrographolide, and both early and late apoptotic rates increased significantly compared to the controls, all in a concentration-dependent manner. Bax and caspase-3 expressions were markedly increased, and Bcl-2 expression was decreased.</p><p><b>CONCLUSIONS</b>Andrographolide inhibits BGC-823 cell growth and induces BGC-823 cell apoptosis by up-regulating Bax and caspase-3 expressions and down-regulating Bcl-2 expression. Andrographolide may be useful as a potent and selective agent in the treatment of human gastric cancers.</p>

Expression of aldo-keto reductase family 1 member B10 in gastric cancer tissues and its clinical significance / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the association of AKR1B10 expression in gastric cancer tissues with clinicopathologic features and prognosis of gastric cancer patients.</p><p><b>METHODS</b>Real-time polymerase chain reaction (RT-PCR) was conducted to detect AKR1B10 mRNA expression in gastric cancer and adjacent gastric mucosa tissues (n=36). AKR1B10 protein expression was measured by immunohistochemistry in primary gastric cancer tissues (n=100) and non-tumorous gastric mucosa tissues (n=70).</p><p><b>RESULTS</b>RT-PCR results confirmed that AKR1B10 was significantly down-regulated in gastric cancer tissues compared with that in paired adjacent mucosa [8.3% (3/36) vs. 91.7% (33/36), P=0.000]. Immunohistochemistry revealed that the percentage of AKR1B10 positive specimens in gastric carcinoma was lower than that in normal specimens [33.0% (33/100) vs. 92.9% (65/70), P=0.000]. The frequencies of positive AKR1B10 in patients was significantly correlated with tumor size (P=0.000), invasive depth (P=0.004), lymph node metastasis (P=0.028), distant metastasis (P=0.031) and TNM stages (P=0.000). The 5-year survival rate of positive AKR1B10 group was significantly higher as compared to negative group (60.6% vs. 32.8%, P<0.01).</p><p><b>CONCLUSION</b>The down-regulation of AKR1B10 expression in gastric cancer may be associated with the progress of gastric cancer is suggestive of poor prognosis.</p>

Association of SOX9 expression and prognosis in patients with gastric cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the association of SOX9 expression and clinicopathologic factors and prognosis of gastric cancer.</p><p><b>METHODS</b>A retrospective cohort study including 112 gastric cancer patients admitted to the Zhejiang Provincial People's Hospital from 2004 to 2006 was performed. Immunohistochemical analysis was used to evaluate the expression of SOX9 in the 112 specimens of gastric cancer tissues and 70 non-cancerous tissues adjacent to the tumor.</p><p><b>RESULTS</b>Low expression of SOX9 was seen in 5(7.1%) tissues out of 70 non-cancerous tissues adjacent to the tumor. A total of 94(83.9%) patients had varying expression of SOX9, of whom 51(45.4%) had overexpression. Univariate analysis demonstrated that the expression of SOX9 was significantly associated with Lauren classification (P<0.05), tumor invasion(P<0.01), lymph node metastasis(P<0.05), distant metastasis(P<0.05) and tumor stage(P<0.05), however there was no significant association between SOX9 expression and sex, age, histological type, histology differentiation or tumor size. Kaplan-Meier analysis showed that the 5-year survival rate of patients with SOX9 over-expression was significantly lower than that of patients with low expression(29.4% vs. 49.2%, P=0.031). Multivariate Cox regression analysis showed that histology differentiation(P=0.046), tumor invasion(P=0.001), and distant metastasis(P<0.01) were independent prognostic factors for gastric cancer, however the over-expression of SOX9 was not significant(P=0.948).</p><p><b>CONCLUSIONS</b>The expression SOX9 is associated with the growth, invasion, and metastasis of gastric cancer, as well as the prognosis. However, SOX9 expression is not an independent factor for the prognosis in patients with gastric cancer.</p>

Laparoscopic versus open wedge resection for gastrointestinal stromal tumors of the stomach: a clinical controlled study / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To compare the surgical outcomes between laparoscopic and open wedge resection for gastrointestinal stromal tumors of the stomach.</p><p><b>METHODS</b>Clinical data of 18 cases undergoing laparoscopic wedge resection from June 2000 to August 2009 at the Zhejiang Provincial People's Hospital were compared with 30 patients treated by open surgery. The perioperative parameters and prognosis data of the two groups were compared.</p><p><b>RESULTS</b>Compared to the open group, laparoscopic group was found with longer operative time, less blood loss, less requirement of postoperative analgesia, earlier resumption of oral intake, earlier return of first flatus, and shorter postoperative hospital stay(all P<0.05). There were no postoperative deaths in both groups. Postoperative complication rate was significantly lower in the laparoscopic group(5.5% vs. 33.3%, P<0.05). The postoperative recurrence rates were 11.8%(2/17) and 10.7%(3/28); the 5-year survival rates were 78% and 63%, respectively, and the difference was not statistically significant(P>0.05).</p><p><b>CONCLUSION</b>Laparoscopic wedge resection is a feasible treatment option for GISTs of the stomach.</p>

Empirical study of oridonin-induced gastric cancer cells MKN45 apoptosis / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the growth inhibition and apoptosis of gastric cancer cell MKN45 induced by oridonin and its mechanism.</p><p><b>METHODS</b>The MTT method was used to investigate the inhibitory effect of oridonin on MKN45 cells. The AO/EB and Hoechst 33258 staining were used to observe the cell morphologic changes of apoptosis induced by oridonin. Prophase apoptotic ratio and cell cycle change were evaluated by GuavaEasycyte PCA-96 system. The expressions of Bcl-2, Bax and caspase 3 proteins were determined by Western blot.</p><p><b>RESULTS</b>Oridonin significantly inhibited the proliferation of MKN45 cells in dose- and time-dependent manner. Typical apoptotic features of the cells treated with oridonin were found by AO/EB and Hoechest33258 staining. When MKN45 cells were treated with different doses of oridonin for 12 h, the prophase apoptotic ratio was stepped up from 3.3% (untreated group) to 8.7%-17.9%; after 24 h, from 4.8% (untreated group) to 13.9%-29.3%. There was significant difference between treated and untreated groups (P <0.01). After treatment with oridonin for 24 h, MKN45 cells were arrested at G(2)/M phase. Western blot analysis showed up-regulated expression of Bax and caspase-3, and no significant change of Bcl-2, but Bcl-2/Bax ratio decreased significantly.</p><p><b>CONCLUSIONS</b>Oridonin significantly inhibits the proliferation of MKN45 cell. Apoptosis of MKN45 induced by oridonin may be associated with the up-regulated expression of Bax and the change of Bcl-2/Bax ratio, thus to activate the caspase pathway.</p>

Effects of anti-heparanase antibody on the growth and invasion of HCCLM6 human hepatocellular carcinoma cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the effects of the self-developed anti-heparanase polypeptide antibodies on growth and invasion of human hepatocellular carcinoma HCCLM6 cells.</p><p><b>METHODS</b>Using MTT, flow cytometry, plate clone formation, transwell invasion and heparan degrading enzyme assay, the growth and invasion changes of human hepatocellular carcinoma HCCLM6 cells by co-culture with each of three self-developed rabbit anti-heparanase polyclonal antibodies were detected.</p><p><b>RESULTS</b>Compared with normal rabbit IgG, in the presence of each anti-heparanase polypeptide antibody, the growth, cell cycle and clone formation remained unchanged, and under the P1 or P2 anti-heparanase polypeptide antibody (with final concentration 100 microg/ml), the cell invasiveness was inhibited by 52.5% and 36.6%, respectively, and the heparanase activity was inhibited by 42.9% and 39.1%, respectively.</p><p><b>CONCLUSION</b>The P1 and P2 anti-heparanase polypeptide antibodies can effectively inhibit the invasion ability and heparanase activity of liver cancer HCCLM6 cells. However, All the three antibodies have no effects on its growth, cell cycle and clone formation.</p>

Relationship between the expression of vascular endothelial growth factor, fms-like tyrosine kinase-1 and biological behavior in gastric carcinoma / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the relationship between the expression of vascular endothelial growth factor (VEGF) and fms-like tyrosine kinase (Flt-1) mRNA and tumor progression, microvessel density and survival time in gastric carcinoma.</p><p><b>METHODS</b>In situ hybridization and immunohistochemical techniques were used to detect the gene expression of VEGF, Flt-1 and CD34 in 118 gastric carcinoma specimens.</p><p><b>RESULTS</b>In situ hybridization revealed that positive expression rates of VEGF and Flt-1 mRNA in gastric carcinoma were 54.24% and 55.9% respectively. There was a significant correlation between the expression of VEGF and Flt-1 mRNA and growth pattern, the depth of tumor invasion, vessel invasion, lymph node and distant metastasis (P < 0.01). The mean tumor microvessel densities (MVD) in patients of stage T3-T4 or those with vessel invasion, lymph node and distant metastases were significantly higher than those of stage T1-T2 and without metastases (P < 0.01). MVD value was correlated with the expression levels of VEGF and Flt-1 mRNA (P < 0.01). The mean survival time and survival rate of patients with positive mRNA expression and mean MVD value >or=54.9/mm2 were significantly lower than those of patients with negative mRNA expression and mean MVD value < 54.9/mm2.</p><p><b>CONCLUSIONS</b>The expression of VEGF and Flt-1 can promote tumor angiogenesis and contribute to tumor invasion and metastasis in gastric carcinoma. VEGF and Flt-1 may serve as valuable indicators of biological behaviour, prognosis and target of gene therapy in gastric carcinoma.</p>

Effect of angiogenesis inhibitor SU6668 on the growth and metastasis of gastric cancer in SCID mice / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To study the effect of angiogenesis inhibitor SU6668 on the growth and metastasis of gastric cancer in SCID mice.</p><p><b>METHODS</b>Metastatic model was established by orthotopic implantation of histologically intact human tumor tissue into the gastric wall of SCID mice. Forty-eight mice were randomly divided into four groups, and saline, 5-FU, SU6668, and 5-FU plus SU6668 were administered by i.p. every day for 6 weeks after tumor implantation. The mice were killed and tumor weight, tumor inhibition rate, intratumoral microvessel density(MVD), apoptotic index(AI) and metastasis inhibition were evaluated.</p><p><b>RESULTS</b>Compared with the control, tumor growth was significantly inhibited in mice treated respectively with 5-FU, SU6668 and 5-FU plus SU6668 with inhibition rates of 47.5%, 64.1% and 69.2% respectively. Decreased MVD and increased AI were noted in the mice treated with SU6668 and 5-FU plus SU6668. The incidences of liver and peritoneal metastases was significantly inhibited and decreased to 62.5%, 69.9% in SU6668 group, and 74.9%, 90% in 5-FU plus SU6668 group. The growth and metastasis of human gastric cancer implanted in SCID mice were significantly inhibited in SU6668 group and combined group, especially in combined group.</p><p><b>CONCLUSION</b>Angiogenesis inhibitor SU6668 has a strong inhibitory effect on tumor growth and metastasis of human gastric cancer transplanted in SCID mice, and has synergistic effect combined with cytotoxic agents.</p>