Magnoflorine inhibits human gastric cancer progression by inducing autophagy, apoptosis and cell cycle arrest by JNK activation regulated by ROS.

The antitumor effect of magnoflorine (Mag), an alkaloid isolated from Coptidis Rhizoma, in gastric cancer (GC) cells has not been reported. In the study, Mag suppressed the proliferation of GC cells, but showed no influence on normal gastric cells. Mechanistically, Mag induced autophagy in GC cells, as evidenced by the up-regulated expression of LC3B-II and increased autophagosome formation. Furthermore, we found that Mag-triggered autophagic cell death was regulated by reactive oxygen species (ROS)-induced suppression of serine/threonine-protein kinases (AKT) signaling. What's more, Mag treatment led to apoptosis in GC cells through enhancing cleaved Caspase-3 and PARP expressions. In addition, up-regulated expression of p27 and p21, as well as down-regulated expression of Cyclin-A and Cyclin-B1 was detected in Mag-treated GC cells, contributing to the S/G2 cell cycle arrest. Importantly, Mag incubation resulted in a significant increase in jun N-terminal kinase (JNK) phosphorylation but not p38 and ERK1/2, which was involved in the modulation of apoptosis and S/G2 phase arrest. Moreover, ROS production was highly induced by Mag treatment, and Mag-exhibited these functions was largely dependent on the generation of ROS in GC cells. Consistently, the GC cell xenograft mouse model confirmed the anti-tumor role of Mag in vivo. Collectively, these results indicated that Mag showed anti-GC effects, which could be a potential therapeutic target for GC treatment.

RP11­619L19.2 promotes colon cancer development by regulating the miR­1271­5p/CD164 axis.

Colon cancer (CC) is one of the leading causes of cancer­related mortality in China and western countries. Several studies have demonstrated that long non­coding RNAs (lncRNAs) play critical roles in cancer development. However, the function of lncRNA RP11­619L19.2 in colon cancer remains unclear. The aim of the present study was to investigate the expression pattern, function and underlying mechanism of action of RP11­619L19.2 in CC development and metastasis. RP11­619L19.2 was found to be highly expressed in CC tissues and cell lines, and it was associated with advanced TNM stage and lymph node metastasis. Furthermore, knockdown of RP11­619L19.2 inhibited CC cell proliferation, migration, invasion and epithelial­to­mesenchymal transition (EMT). It was also observed that RP11­619L19.2 was reciprocally repressed by miR­1271­5p. Of note, miR­1271­5p negatively regulated CD164 expression by directly targeting the 3'­untranslated region of CD164. Overexpression of CD164 reversed the antimetastatic activity of RP11­619L19.2 knockdown in CC cells. Mechanistically, it was demonstrated that lncRNA RP11­619L19.2 played an oncogenic role and promoted CC development and metastasis by regulating the miR­1271­5p/CD164 axis and EMT. In conclusion, the findings of the present study indicated that RP11­619L19.2 regulates CD164 expression and EMT by sponging miR­1271­5p, which may provide novel targets for lncRNA­directed diagnosis and therapy for patients with CC.

Knockdown of TMPRSS3 inhibits gastric cancer cell proliferation, invasion and EMT via regulation of the ERK1/2 and PI3K/Akt pathways.

The transmembrane protease, serine 3 (TMPRSS3), a member of the type II transmembrane serine protease family, plays an important role in mediating tissue development, homeostasis and various biological processes. Recently, TMPRSS3 has been reported to be involved in cancer progression. However, the role of TMPRSS3 in gastric cancer (GC) remains largely unknown. In this study, we found that TMPRSS3 was highly expressed in GC tissues and cell lines. Knockdown of TMPRSS3 inhibited GC cell proliferation, invasion and epithelial-mesenchymal transition (EMT) in vitro as well as suppressed GC cell growth and dissemination in vivo. These inhibitory effects were mediated by regulation of the ERK1/2 signaling pathway. Moreover, TMPRSS3-mediated ERK1/2 activation was dependent on the PI3K/Akt pathway. In conclusion, TMPRSS3 contributed to GC progression via activation of the PI3K/Akt/ERK signaling pathway and might act as a therapeutic target for GC treatment.

[The features of pathology and immunohistochemistry in orbital meningiomas].

OBJECTIVE: To study the biological characteristics of orbital meningiomas using histological and immunohistochemistrical analysis. METHODS: 19 specimens taking from orbital meningiomas were included in the study. HE staining was used for histology analysis and the immunohistochemistry was applied to demonstrate the expression of Vimentin, EMA, Ki-67, p53 in the tissue of orbital meningiomas. RESULTS: The main configuration of orbital meningiomas was meningothelial, transitional and fibrous meningioma. The expression rations of Vimentin and EMA were 94.75% (18/19), 52.63% (10/19), respectively. The detected rations of Ki-67 and p53 were very lower. CONCLUSIONS: Our study shows that the major histological configuration of orbital meningiomas are meningothelial, transitional and fibrous meningioma. Compare with intracranial meningiomas, the expression rate of EMA in orbital meningiomas is lower. No difference of the expression rates of p53 and Ki-67 are found in benignant, recrudescent and malignant of tumor.

[Analysis of the common morphological characteristics of cancerous cells using atomic force microscope].

OBJECTIVE: To observe the surface ultrastructure of different tumor cells in vivo using atomic force microscope (AFM) and analyze their common characteristics. METHODS: We selected 60 specimens of each of normal liver cells, liver cancer, cervical squamous cells, cervical cancer cells, ductal epithelial cells and breast cancer cells for scanning using AFM. The cell surface scan images were analyzed using image analysis software to identify their common morphological features. RESULTS: From normal cervical squamous epithelial cells, intermediate cells, and basal cells to HPV-infected cells, CIN2-3 cells and cervical cancer cells, the membrane surface roughness became gradually increased (P<0.05). Similarly, the surface roughness increased significantly in the order of normal liver cells, hepatitis B cirrhosis liver cells, and hepatocellular carcinoma cells (P<0.05). The average surface roughness also tended to increase from normal mammary gland cells to mammary gland hyperplasia cells and breast cancer cells (P<0.05). CONCLUSION: Normal cells and tumor cells show different cell membrane morphologies, and such morphological features provide a reliable basis for clinical pathological diagnosis and differential diagnosis of malignancies.

[Role of vascular endothelial growth factor in rats with severe acute pancreatitis].

OBJECTIVE: To investigate the role of vascular endothelial growth factor (VEGF) in the pathogenesis of severe acute pancreatitis (SAP) in rats. METHODS: Sixty-four male SD rats were randomly divided into control group and SAP group, and in the latter group, SAP was induced by retrograde injection of 5% sodium taurocholate in the pancreaticobiliary duct. The rats were sacrificed at 1, 3, 6 and 12 h after the operation, and the severity of pancreatitis was assessed according to histological scoring. The serum levels of VEGF were examined with enzyme-linked immunosorbent assay, and the expression of VEGF in the pancreatic tissues was measured by SP immunohistochemistry. Another 30 SD rats were randomized into the control group, SAP group and SAP+recombinant rat VEGF injection group, and the vascular permeability of the pancreatic microcirculation was determined by Evans Blue leakage test. RESULTS: At each of the time points for measurement, both the serum VEGF level and scores of pancreatic tissue injury were significantly higher in SAP group than in the control group (P<0.05). Compared with the control group, the expressions of VEGF in the pancreatic tissues of SAP group were significantly up-regulated following the operation (P<0.05). The vascular permeability of the pancreatic microcirculation significantly increased after the onset of SAP, and injection of recombinant rat VEGF significantly increased the leakage rate of Evans Blue. CONCLUSION: VEGF may play an important role in the pathogenesis of pancreatitis and in causing edema and hemorrhage in SAP, and the level of serum VEGF may reflect the severity of pancreatic injury.

[Protective effects of captopril against lung injury in rats with severe acute pancreatitis].

OBJECTIVE: To investigate the protective effects of captopril against lung injury in a rat model of severe acute pancreatitis (SAP). METHODS: Seventy-two male SD rats were randomized into sham-operated group (SO group), SAP group and captopril intervention group (CAP group). Serum amylase and myeloperoxidase (MPO) activity in the lung tissue were examined at 1, 6 and 12 h after the operation. TNF-α and AngII in the lung tissue were detected by ELISA, and the histopathological changes of the pancreas and lung were observed microscopically. RESULTS: The MPO activity , which was similar between SAP group and CAP group at 1 h, were significantly lowered in CAP group at 6 and 12 h (P<0.05). Serum amylase level and the levels of TNF-α and AngII in the lung tissue homogenate were all reduced significantly in CAP group as compared to those in SAP group (P<0.01). The pathological injury of the lung was obviously lessened in CAP group in comparison with that in SAP group. CONCLUSION: Captopril can ameliorate SAP-induced lung injury in rats.