Research Progress on Correlation of Glucose Metabolism Mechanism with Invasion and Metastasis of Nasopharyngeal Carcinoma Cells / 肿瘤防治研究

Metastasis is the main cause of cancer-related death. Growing evidence has shown that changes in glucose metabolism in nasopharyngeal carcinoma cells affect the invasion and metastasis of nasopharyngeal carcinoma through many pathways. This review summarizes the molecular mechanism underlying abnormal glucose metabolism in nasopharyngeal carcinoma cells and analyzes its relationship with the invasion and metastasis of nasopharyngeal carcinoma, including aerobic glycolysis, aerobic oxidation, and pentose phosphate pathway. The aim is to provide novel approaches using the relationships among glucose metabolism, invasion, and metastasis in the targeted therapy of nasopharyngeal carcinoma.

Mechanism of Pachymic Acid in Inhibiting Invasion and Metastasis of Renal Carcinoma Cells via Regulating MMP/TIMP Balance by Smads / 中国实验方剂学杂志

ObjectiveTo investigate the effect and mechanism of pachymic acid （PA） in Poria on the invasion and metastasis of renal carcinoma cells. MethodThe effect of PA （0， 20， 40， 80， 160 μmol·L-1） on cell viability was detected by cell counting kit-8（CCK-8）， and the dose of PA was selected for subsequent experiments. The effect of PA （0， 20， 40， 80 μmol·L-1） on cell proliferation was evaluated by colony formation assay. The effect of PA （0， 20， 40， 80 μmol·L-1） on cell adhesion ability was observed by cell adhesion assay. The effect of PA （0， 20， 40， and 80 μmol·L-1） on cell invasion and metastasis was investigated by Wound healing assay and Transwell invasion assay. The inhibitory effect of PA （0， 20， 40， 80 μmol·L-1） on cell motility was further observed and verified by high-content imaging technology. The effects of PA （0， 20， 40， 80 μmol·L-1） on the expression of matrix metalloproteinase （MMP）/tissue inhibitor of metalloproteinasas （TIMP） related to invasion and metastasis and Smads were detected by Western blot. ResultCCK-8 results showed that compared with the blank group， the PA groups showed decreased cell viability（P<0.01）， with the half-maximal inhibitory concentration （IC50） of ACHN cells of 70.42 μmol·L-1 at 24 h. Colony formation assay showed that the number of cell clonal groups in the PA groups was reduced compared with that in the blank group（P<0.01）. Cell adhesion assay showed that compared with the blank group， the PA groups displayed reduced cell adhesion（P<0.01）. Wound healing assay showed that the wound healing rate of cells in the PA groups was lower than that in the blank group （P<0.05，P<0.01）. Transwell invasion assay showed that compared with the blank group， the number of transmembrane cells in PA groups was reduced（P<0.01）. High-content imaging showed that the cumulative migration distance of cells in the PA groups was shorter than that in the blank group（P<0.01）. The results of Western blot showed that the protein expression of MMP-2 and MMP-9 in the PA groups decreased （P<0.01）， and TIMP-1 protein expression increased （P<0.01） compared with those in the blank group. In addition， compared with the blank group， the PA groups showed decreased protein expression of Smad2 and Smad3 （P<0.01）. ConclusionPA can inhibit the invasion and metastasis of renal carcinoma cells presumably through regulating the homeostasis of MMP/TIMP by Smad2/3.

Research Progress of Pseudogenes in Hepatocellular Carcinoma / 肿瘤防治研究

Pseudogenes were initially thought to have no function and were called by aliases, such as "junk genes." With the emergence of large-scale genomics projects and more and more experimental studies, pseudogenes have been shown to play an important role in the occurrence and development of solid tumors, especially playing an important regulatory role in the occurrence and develepment of liver cancer, such as regulating the proliferation, apoptosis, invasion, metastasis, and immunity of liver cancer cells. Recent studies showed that pseudogenes can act as regulators of oncogenes and tumor suppressors in hepatocellular carcinoma (HCC) and can thus serve as prognostic markers and even therapeutic targets for this cancer type. In this review, we systematically summarize the mechanisms and functions of different pseudogenes in HCC and present their future prospects as therapeutic targets.

Mechanism of action of lactic acid in tumor microenvironment and related treatment / 国际肿瘤学杂志

Lactic acid, a widespread metabolite in the tumor microenvironment, is mainly produced by tumor cells that undergo aerobic glycolysis. Lactic acid is closely related to the occurrence and development of tumor. It not only serves as a substrate to supply energy to tumor cells, but also acts as a signaling molecule to activate multiple pathways to promote invasive and metastasis, angiogenesis and immune escape of tumor cells. In-depth research on the mechanism of action of lactic acid in the occurrence and development of tumor and related therapeutic progress will help to find drug targets for treatment of tumor and improve prognosis of patients.

Expression of miR-101-3p in Gastric Cancer and Its Effects on Invasion, Metastasis, and Angiogenesis of Gastric Cancer Cells by Targeting STC-1 Gene to Regulate PI3K/AKT Signaling Pathway / 肿瘤防治研究

Objective To explore the expression of miR-101-3p in gastric cancer and its mechanism on the invasion, metastasis, and angiogenesis of gastric cancer cells by targeting the STC-1 gene to regulate the PI3K/AKT signaling pathway. Methods qRT-PCR was used to detect the expression of miR-101-3p and STC-1 mRNA in gastric cancer tissues and BGC-823 cell and analyze the relationship between miR-101-3p expression and patients' clinical pathological factors. The cells were transfected with miRNA mimics and plasmids separately or in combination with LipofectamineTM 2000. TargetScanHuman prediction and dual-luciferase assay were used to verify the targeted regulation of miR-101-3p on STC-1. The effect and possible mechanism of miR-101-3p targeting the STC-1 gene on the invasion, metastasis, and angiogenesis of cancer cells were verified by scratch test, Transwell chamber test, Matrigel in vitro tube forming test, and Western blot assay. The development of the transplanted tumor was detected by nude mouse tumorigenicity test. Results The expression of STC-1 in gastric cancer tissues was higher than that in normal tissues. Compared with normal gastric tissues and GES-1 cells, miR-101-3p was down-regulated, and STC-1 mRNA was up-regulated in gastric cancer tissues and BGC-823 cell. The level of miR-101-3p was negatively correlated with the level of STC-1, and significantly correlated with the degree of tumor differentiation, TNM stage, and lymph node metastasis (P < 0.05). miR-101-3p directly targeted STC-1. The overexpression of miR-101-3p inhibited STC-1 expression and downregulated the expression of p-PI3K/PI3K, p-AKT/AKT, MMP-2, MMP-9, VEGF, and Ang2, consequently, inhibited tumor cell invasion, metastasis, and angiogenesis and reduced the size and weight of the transplanted tumors (P < 0.05). Conclusion miR-101-3p is down-regulated in gastric cancer and can target the STC-1 gene to regulate the PI3K/AKT signaling pathway and inhibit the invasion, metastasis, and angiogenesis of BGC-823 gastric cancer cells and the development of transplanted tumors in vivo.

Research Progress on Influence of DNA Methylation on Signal Pathways Related to Invasion and Metastasis of Nasopharyngeal Carcinoma / 肿瘤防治研究

Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors of the head and neck region. NPC has the characteristics of insidious onset, strong invasiveness and early lymph node metastasis. A variety of signaling pathways play a role in the invasion and metastasis of nasopharyngeal carcinoma, but the specific mechanism has not yet been fully elucidated. Recent studies have found that DNA methylation of nasopharyngeal carcinoma-related genes can affect the invasion and metastasis of nasopharyngeal carcinoma through a variety of signaling pathways including Wnt/β-catenin, PI3K/AKT and MAPK signaling pathways. This article reviews the specific mechanism of DNA methylation affecting the invasion and metastasis of nasopharyngeal carcinoma through the above-mentioned signaling pathways.

MiR-4484 regulates the expression of integrin α 6 in gastric cancer tissues and its significance / 中华肿瘤杂志

Objective: To investigate the relationship between the expression of integrin α 6 (ITGA6), miR-4484 and the pathologic stage of gastric cancer. Methods: Gastric cancer tissues and normal gastric mucosa tissues adjacent to cancer (>5 cm from tumor margin) of 30 patients with primary gastric cancer who underwent direct surgical resection without adjuvant therapy from June to September 2017 in West China Hospital of Sichuan University were selected. Real-time quantitative polymerase chain reaction (PCR) was used to detect the expression levels of miR-4484 and ITGA6, western blot was used to detect the expression level of ITGA6 protein, dual luciferase reporter gene was used to verify the relationship between ITGA6 and miR-4484. Spearman's correlation analysis was used to determine the relationship between miR-4484 and ITGA6 expression levels in gastric cancer tissues. Results: The expression level of ITGΑ6 in gastric cancer (32.30±13.47) was higher than that in matched normal gastric tissues (24.55±10.25, P=0.015), the area under the receiver operating characteristic (ROC) curve was 0.660 and the diagnostic sensitivity and specificity were 43.3% and 96.7%, respectively. The expression level of miR-4484 in gastric cancer (4.11±2.87) was lower than that of matched normal gastric tissues (5.75±2.80, P=0.029), the area under the ROC curve was 0.690 and the diagnostic sensitivity and specificity were 30.0% and 86.7%, respectively. The expression level of miR-4484 was negatively correlated with ITGA6 in gastric cancer tissues (r=-0.621, P<0.001). The expression level of ITGA6 protein in gastric cancer tissues (0.65±0.19) was higher than that in normal adjacent tissues (0.26±0.12, P<0.001). Compared with ITGA6 3'UTR wild-type+ miR-NC group, ITGA6 3'UTR wild-type+ miRNA mimics group had lower luciferase activity (50.69±5.10, 34.00±1.19, P<0.001), while the luciferase activity of ITGA6 3'UTR wild-type+ ASO miR-4484 group was higher than that of ITGA6 3'UTR wild-type+ miR-NC group (82.44±6.37, 50.69±5.10, P<0.001), indicated that ITGA6 was the direct target gene of miR-4484. The expression levels of miR-4484 in T1, T2, T3 and T4 (4a and 4b) gastric cancer tissues were 9.98±2.24, 5.28±2.03, 2.92±2.04 and 4.11±2.87, respectively, with statistical significance (P<0.001). The expression levels of ITGA6 in N0, N1, N2 and N3 gastric cancer tissues were 29.55±8.32, 21.71±3.75, 24.60±8.79 and 40.69±15.83, respectively, with statistical significance (P=0.022). The expression levels of miR-4484 in N0, N1, N2 and N3 gastric cancer tissues were 5.01±3.52, 5.48±2.76, 5.88±1.83 and 2.30±1.56, respectively, with statistical significance (P=0.032). The expression levels of ITGA6 in M0 and M1 gastric cancer tissues were 26.28±7.66 and 52.08±8.12, respectively, with statistical significance (P<0.001). The expression levels of miR-4484 in M0 and M1 gastric cancer tissues were 4.95±2.74 and 1.34±0.80, respectively, with statistical significance (P<0.001). Conclusions: ITGA6 is upregulated in gastric cancer tissues, while miR-4484 is downregulated in the gastric cancer group, and its expression level is related to the clinicopathological features of gastric cancer. ITGA6 is the direct target gene of miR-4484, implicates that miR-4484 may inhibit the invasion and metastasis of gastric cancer by regulating the expression of ITGA6. Both miR-4484 and ITGA6 may be the new prognostic markers and potential therapeutic targets of gastric cancer.

Xiao Xianxiongtang Regulates Ca2+ Load and Inhibits Epithelial-mesenchymal Transition， Invasion， and Migration of MGC-803 Cells： Based on Wnt5a/ Ca2+/NFAT Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the effect of Xiao Xianxiongtang （XXXT） on the transforming growth factor （TGF）-β1-induced invasion， metastasis， and epithelial-mesenchymal transition （EMT） of gastric cancer MGC-803 cells and the underlying mechanism. MethodThe molecular docking between XXXT and nuclear factor of activated T cells （NFAT） was performed by CB-DOCK （http：//clab.labshare.cn/cb-dock/）. The invasion and metastasis model of MGC-803 cells was established with 10 μg·L-1 TGF-β1. MGC-803 cells were classified into blank group， model group， 0.1 g·L-1 XXXT group， 0.2 g·L-1 XXXT group， and 0.4 g·L-1 XXXT group. For further clarifying the key role of Wnt5a/Ca2+/NFAT signaling pathway in the inhibition of XXXT on gastric cancer， MGC-803 cells were transfected with Wnt5a overexpression plasmid， and then the cells were classified into blank plasmid group， Wnt5a-OE group， blank plasmid + XXXT （0.4 g·L-1） group， and Wnt5a-OE + XXXT （0.4 g·L-1） group. Cell viability was determined by cell counting kit-8 （CCK-8） assay， cell invasion and migration ability by Transwell invasion assay and wound healing assay， expression of EMT-related proteins （E-cadherin， N-cadherin， Vimentin， Snail） and Wnt5a/Ca2+/NFAT signaling pathway-related key proteins ［Wnt5a， calcineurin （CaN）， NFAT1， and p-NFAT1］ by Western blot， and changes in intracellular Ca2+ concentration by immunofluorescence assay. ResultMolecular docking suggested that XXXT acted on Wnt5a/Ca2+/NFAT signaling pathway. XXXT （0.1， 0.2， 0.4 g·L-1） significantly promoted the loss of MGC-803 cell viability （P<0.05，P<0.01）. It inhibited cells from invading the transwell lower chamber and slowed down the healing of cell wounds in a dose-dependent manner （P<0.05， P<0.01）. Moreover， it promoted the expression of E-cadherin while suppressed the expression of N-cadherin， Vimentin， and Snail （P<0.05， P<0.01）. Further experiments showed that XXXT could inhibit the expression of Wnt5a， CaN， NFAT1， and p-NFAT1， and reduce the nuclear expression of NFAT1 and the transcription activity mediated by NFAT1， so as to reduce the cellular Ca2+ concentration （P<0.05， P<0.01）. XXXT can reverse the effect of Wnt5a （P<0.05， P<0.01）. ConclusionXXXT can attenuate the invasion， metastasis， and EMT of MGC-803 cells via the Wnt5a/Ca2+/NFAT pathway， thereby weakening the tumor-promoting effect of TGF-β1. In summary， XXXT may exert therapeutic effect on gastric cancer by regulating the invasion， metastasis， and EMT of gastric cancer cells.

miR-325-3p Regulates Epithelial-mesenchymal Transition, Invasion and Metastasis of Gastric Cancer via Targeting CLDN1 Gene / 肿瘤防治研究

Objective To investigate the effects of miR-325-3p on the EMT, invasion and metastasis of gastric cancer cells by targeting CLDN1 gene. Methods We selected human gastric epithelial cell lines GES-1 and gastric cancer cell lines HGC27, SGC-7901, MKN-45 and MGC-803, and detected the expression of miR-325-3p and CLDN1. The targeting relation between miR-325-3p and CLDN1 were verified by dual luciferase report experiments, and the expression of miR-325-3p and CLDN1 in gastric cancer cells were intervened. qRT-PCR and Western blot were adopted to detect N-cadherin, vimentin and MMP2 expression in cells. CCK-8 assay, Transwell assay, flow cytometry were utilized to detect cell proliferation activity, invasion and apoptosis, respectively. Results Compared with GES-1 cells, miR-325-3p expression was decreased while CLDN1 expression was increased in MGC-803 cells (P < 0.05). CLDN1 was a target gene of miR-325-3p. Overexpression of miR-325-3p could inhibit the proliferation, invasion and EMT of gastric cancer cells, while promote the apoptosis of gastric cancer cells. However, the inhibition of miR-325-3p had the opposite effect (P < 0.05). The overexpression of CLDN1 could reverse the effect of miR-325-3p overexpression on the biological behavior of gastric cancer cells. Conclusion miR-325-3p can suppress CLDN1, inhibit the invasion, metastasis and EMT while promote the apoptosis of gastric cancer cells. miR-325-3p is expected to be a new target in gastric cancer treatment.

miR-144-3p Inhibits the Invasion and Metastasis of Lung Adenocarcinoma Cells by Targeting IRS1 / 中国肺癌杂志

BACKGROUND@#MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression, influence cellular processes, and promote disease development. Variations in miRNA expression have been observed in many diseases, including hepatitis, cardiovascular disease, and cancer. The aim of this study is to investigate the effect of miR-144-3p on the invasion and metastasis of lung adenocarcinoma by targeting recombinant insulin receptor substrate 1 (IRS1).@*METHODS@#The expression of miR-144-3p in patients with lung adenocarcinoma was queried through bioinformatics database. MirTarPathway was used to analyze the KEGG enrichment pathway of miRNA. The expression and plasmid transfection efficiency of miR-144-3p in lung adenocarcinoma cell lines were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Transwell assay was used to detect the changes of cell invasion and migration ability in different groups. Bioinformatics determined the key genes (Hub genes) of miR-144-3p; Double luciferase target assay was used to detect the mutual binding of miR-144 and IRS1. Western blot assay was used to detect the expression of IRS1 in different cell lines and the expression of after overexpression of miR-144.@*RESULTS@#The expression of miR-144-3p in lung adenocarcinoma tissues was decreased, qRT-PCR results indicated that the expression of miR-144-3p in lung adenocarcinoma cell A549 was significantly decreased (P<0.05), and the overexpressed plasmid was successfully transfected (P<0.05). Overexpression of miR-144 decreased the ability of cell migration and invasion (P<0.05). The expression of IRS1 was up-regulated in lung adenocarcinoma tissues. Survival analysis showed that patients with lung adenocarcinoma with high IRS1 expression had a poor prognosis (P<0.05). Double luciferase assay results showed that miR-144 could specifically identify 3'-UTR of IRS1 and inhibit reporter enzyme expression (P<0.05). Western blot indicated that the expression of IRS1 was increased in A549 cells (P<0.05). After overexpression of miR-144, the expression level of IRS1 protein was decreased (P<0.05). Transwell experiment proved that miR-144-3p could inhibit invasion and metastasis of lung adenocarcinoma cells by targeting IRS1 (P<0.05).@*CONCLUSIONS@#MiR-144-3p inhibits the invasion and migration of A549 cells through targeted regulation of IRS1, thus playing an anticancer role in tumors.

Inhibitory Effect of Weichang'an Granule on Invasion and Metastasis of MKN45 Cells in Human Gastric Cancer by RUFY3 / 中国实验方剂学杂志

Objective:To explore the molecular mechanism of spleen-strengthening traditional Chinese medicine （TCM） Weichang'an granule in inhibiting the invasion and metastasis of human gastric cancer MKN45 cells. Method:MKN45 cells were cultured <italic>in vitro</italic> and incubated with different concentrations（600， 900， 1 200， 1 500 mg·L^-1）of Weichang'an granule for 24， 48， 72 h. Cell counting kit-8 （CCK-8） assay was used to detect its effect on the cell proliferation. Western blot was used to detect the expression of RUN and FYVE domain containing 3（RUFY3） in normal gastric mucosa cells and different gastric cancer cell lines. The expression of RUFY3 in the gastric cancer cells after Weichang'an granule intervention （600， 900， 1 200 mg·L^-1） was detected by Western blot. Lentivirus transfection technique was used to achieve the stable and silenced expression of RUFY3 in gastric cancer MKN45 cells. Transwell assay was used to evaluate the influence of Weichang'an granule and silenced RUFY3 on the metastasis and invasion ability of MKN45. E-cadherin，N-cadherin，Vimentin，Zinc-finger transcription factor （SNAIL1 and SNAIL2） protein expression levels were detected by Western blot. Result:RUFY3 expression in human gastric cancer cells was significantly higher than that in normal gastric mucosa．The protein expression of RUFY3 in MKN45 cells of silenced RUFY3 group was significantly lower than that in Lentivirus negative group （<italic>P</italic><0.01）． Weichang'an granule inhibited the expression of RUFY3 in human MKN45 gastric cancer cells （<italic>P</italic><0.05， <italic>P</italic><0.01） in a concentration-dependent manner. As compared with the blank group， both Weichang'an granule and silenced RUFY3 inhibited the metastasis and invasion ability of MKN45 （<italic>P</italic><0.01）. After Weichang'an granule and silenced RUFY3 treatment， the protein expression of epithelial marker gene E-cadherin was up-regulated （<italic>P</italic><0.01）， the protein expression of Vimentin and N-cadherin decreased， but with no statistical difference，while SNAIL1 and SNAIL2 were both significantly down-regulated （<italic>P</italic><0.01）. Conclusion:By targeting RUFY3 to regulate epithelial mesenchymal transformation， the spleen-strengthening TCM compound Weichang'an granule can inhibit the invasion and metastasis of gastric cancer.

Effect of Endoplasmic Reticulum Stress on Tumorigenesis and Development and Intervention of Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

Endoplasmic reticulum （ER） is an important organelle responsible for protein， steroid， lipid and carbohydrate synthesis and calcium-dependent signal transduction in eukaryotic cells. ER homeostasis is essential for normal cell function. ER homeostasis imbalance can induce ER stress （ERS）， which participates in the occurrence and development of diseases of the digestive system， respiratory system， circulatory system， nervous system， reproductive system， and endocrine system， and affects body health. Among various diseases， cancers seriously endanger people′s health due to its high mortality rate， disability rate， and recurrence rate. Due to the survival characteristics of unlimited proliferation， tumor cells are often exposed to various internal and external stimuli such as hypoxia， ischemia， excessive proliferation， and starvation， which destroy intracellular protein balance and induce ERS to some extent for survival. ERS plays a major role in various tumors and has dual functions in the survival of tumor cells： promoting the survival of tumor cells by activating a series of adaptive responses， while inducing ERS-related apoptosis pathways， so as to promote tumor cell death and inhibit tumor growth and invasion. As multiple functions of ERS in tumors are reported， many scholars have tried to intervene in the progress of tumors from the perspective of ERS. The therapeutic effect of traditional Chinese medicine （TCM） on tumors has been widely recognized. TCM can participate in the regulation of tumors from many aspects， including ERS， chemoradiotherapy resistance， gastrointestinal adverse reactions caused by chemotherapy， postoperative recurrence and metastasis. Since there are few reports on the antitumor effect of TCM from the perspective of ERS， this paper expounds the influence of ERS on tumorigenesis and development and the progress of TCM intervention in tumor through ERS， in order to provide a new direction for tumor treatment.

Mechanical Heterogeneity of Tumor Tissues and Epithelial-Mesenchymal Transition of Tumor Cells / 医用生物力学

In the process of tumor growth, with the proliferation and expansion of cancer cells, the reconstruction of extracellular matrix (ECM) of cancer tissues, the restriction of surrounding tissues and the flow of cancer tissue interstitial fluid, the special stress environment is formed in the tumor tissues. Significant differences are found in the mechanical environment and mechanical characteristics of different regions of tumor tissues, that is, mechanical heterogeneity. The reseach shows that the mechanical properties of tumor tissue invasion frontier areas are more significant and complex. In particular, the epithelial-mesenchymal transition (EMT) of tumor cells also prefers to concentrate on this area. The mechanical stress generated by the invasion front can induce EMT of tumor cells through TWIST1, TGF-β, WNT and other force signal transduction pathways, and promote tumor cell invasion. From the perspective of tumor biomechanics, this review focuses on the relationship between mechanical heterogeneity of tumor cells and EMT, so as to provide the theoretical basis for mechanoenvironment-targeted therapy of tumors.

Progress in antitumor activity of baicalin / 药学学报

Flavonoids baicalin is the main bioactive component extracted from Scutellaria baicalensis Georgi. Baicalin has high medicinal value and shows extensive pharmacological effects including antitumor, antibiosis, anti-inflammatory, antioxidation, neuro-protection, and significant potential in tumor treatment. Recent studies have shown that baicalin suppresses the growth of many kinds of human cancer. The underlying mechanisms include induction of apoptosis, induction of cell cycle arrest, inhibition of tumor metastasis, suppression of angiogenesis, and so on. This article reviewed the research progress of baicalin on its antitumor pharmacology and possible mechanisms at home and abroad, and provided the basis for its further research.

Serum levels of matrix metalloproteinase-2 in patients with oral submucous fibrosis and oral squamous cell carcinoma

Background: Matrix metalloproteinase-2 (MMP-2), which is supposed to enable cancer cells cross the basement membrane and metastasize by selectively cleaving type IV collagen, is anticipated to be a good diagnostic and prognostic marker in oral squamous cell carcinoma (OSCC) and oral submucous fibrosis (OSMF). Thus, the study is aimed to estimate and compare the serum MMP-2 levels in patients with OSMF and OSCC.Methods: The study was conducted on 88 subjects, divided into three groups; Group I (healthy subjects, n=28), Group II (patients with OSMF, n=30), and Group III (patients with OSCC, n=30). Serum levels of MMP-2 were estimated and compared among the groups and further with the clinical parameters within the groups.Results: The mean serum MMP-2 levels in patients with OSMF (2.87±1.04 ng/mL) and with OSCC (11.55±2.16 ng/mL) were significantly higher than the healthy subjects (0.93±0.26 ng/mL) (p <0.0001, for both). Furthermore, the mean serum MMP-2 levels in OSMF subjects had a positive association with inter-incisal opening (IIO), however, there was no association with the degree of burning sensation. Likewise, in subjects with OSCC, levels of serum MMP-2 showed positive association with histopathological grades, however, significant association with the site of occurrence and primary tumor size was not found.Conclusions: Elevated serum MMP-2 levels can be used as a screening tool in the early detection of OSMF and OSCC cases. Moreover, MMP-2 might be a good marker in evaluating the tumor grade in OSCC and the IIO in OSMF.

Association of the co-expression of SOX2 and Podoplanin in the progression of oral squamous cell carcinomas - an immunohistochemical study

Abstract SOX2 is a transcription factor related to the maintenance of stem cells in a pluripotent state. Podoplanin is a type of transmembrane sialoglycoprotein, which plays an important role in tumor progression and metastasis. This study aims to determine association of SOX2 and podoplanin expression in the progression of oral squamous cell carcinomas and to elucidate the association between two proteins. Methodology: The immunohistochemical expression of SOX2 and podoplanin were evaluated in 60 cases of primary oral squamous cell carcinomas. The correlation between the SOX2 and podoplanin expression and the clinicopathological features of the tumors and the patient outcomes were assessed. Results: The expression of SOX2 was seen in 38/60 (63%) of the cases and the expression for podoplanin was seen in 45/60 (75%) cases. There was a significant inverse correlation between the expression of SOX2 and podoplanin with the tumor grade (p=0.002 and p=0.017, respectively). There was a high expression of SOX2 in 9/13 cases that presented with disease free survival. Survival analysis showed that a high expression of SOX2 correlated positively (p=0.043) with the disease-free survival. There was a significant positive association between the pattern of SOX2 and podoplanin expression (p=0.002). Conclusion: A high expression of SOX2 was associated with better disease-free survival. The expression of podoplanin was associated with the degree of differentiation of the tumors. Analysis of these biomarkers can aid in the prognosis and treatment of oral squamous cell carcinomas.

Chemokine receptor CXCR7 assists CXCR4 in modulating the directional metastasis and EMT of pancreatic cancer / 西安交通大学学报(医学版)

Objective: To investigate the effect of CXCL12/CXCR4/CXCR7 axis on the metastasis and invasion in pancreatic cancer so as to provide new evidence for research on pancreatic cancer metastasis treatment. Methods: MiaPaCa-2 cells were transfected with CXCR4 shRNA and CXCR7 shRNA, and the Transwell assay was used to determine the effects of CXCL12/CXCR4/CXCR7 axis on cell invasion and migration. Quantitative RT-PCR and Western blotting were used to explore the effects of CXCL12/CXCR4/CXCR7 axis on the expressions of invasion-related genes (MMP-2 and uPA) and EMT-related genes (E-cadherin and Vimentin). Results: CXCL12 significantly increased the metastasis and invasion of pancreatic cancer cells. The enhancement of tumor cell invasion was effectively countered by CXCR4 shRNA or CXCR7 shRNA. CXCL12/CXCR4 axis in cancer cells increased the expressions of invasion-related genes (MMP-2 and uPA) and EMT-related genes (E-cadherin and Vimentin). CXCL12/CXCR7 axis only increased the expressions of MMP-2 and uPA. Compared to blocking CXCR4 or CXCR7 alone, the inhibitory effects on invasion-related genes and EMT-related genes were more effective when both CXCR4 and CXCR7 were blocked. Conclusion: CXCL12/CXCR4/CXCR7 axis regulates the EMT, metastasis, and invasion of pancreatic cancer cells.

Mechanism of lncRNA CTD-3252C9.4 on invasion and migration of pancreatic cancer Panc-1 cells in vitro / 中国药科大学学报

@#The aim of this study is to investigate the inhibitory effect of long non-coding RNA(lncRNA)CTD-3252C9. 4 on migration and invasion of human pancreatic cancer cell Panc-1 in vitro and its mechanism. Panc-1 cells were stimulated by epidermal growth factor(EGF)in three-dimensional semi-solid system of cultured pancreatic cancer spheres. RT-qPCR was used to detected the transfection efficiency of lncRNA CTD-3252C9. 4. The effects of lncRNA CTD-3252C9. 4 and bone morphogenetix protein 7(BMP7)on the invasion and migration of Panc-1 cells were detected by scratch healing method and Transwell chamber method. The changes of target gene BMP7 and epithelial-mesenchymal transition(EMT)related proteins were verified by Western blot. EGF could significantly inhibit the expression of lncRNA CTD-3252C9. 4 in Panc-1 cells. The lncRNA can affect cells invasion and migration by inhibiting the transcription of the oncogene BMP7, then inhibit the process of EMT of tumors.

Mechanism of Modified Maimendong Tang Combined with Cisplatin in Enhancing Chemosensitivity on Human Lung Adenocarcinoma A549 Cells / 中国实验方剂学杂志

Objective: To observe effect of modified Maimendong Tang combined with cisplatin on the cell proliferation, apoptosis, invasion and metastasis and the protein expressions of Caspase-3, epidermal growth factor receptor(EGFR)of human lung adenocarcinoma A549 cells in vitro, so as to investigate their relevant mechanisms in inhibiting cells proliferation, invasion and metastasis and inducing apoptosis of A549 cells. Method: The lung cancer cells A549 were respectively treated with modified Maimendong Tang(15 g·L-1), cisplatin(9 mg·L-1), and combined drugs. Afterwards, they were divided into control group, modified Maimendong Tang group, cisplatin group and modified Maimendong Tang combined with cisplatin group. Thiazolyl blue tetrazolium bromide (MTT) assay was used to evaluate the proliferation of A549 cells treated with different concentrations of modified Maimendong Tang(0, 5, 10, 15, 20, 25 g·L-1) and cisplatin(0, 3, 6, 9, 12, 15 mg·L-1) for 24, 48, 72 h. The proliferation of A549 cells in each group was detected by MTT assay; flow cytometry was used to detect the degree of apoptosis and cycle in the above four groups of cells; scratch test and transwell migration test were performed to observe the abilities of invasion and metastasis of each group; Western blot was used to detect Caspase-3 and EGFR protein expression. Result: The concentration of modified Maimendong Tang and cisplatin and the time of intervention were negatively correlated with the proliferative capacity of A549 cells (PP0/G1 phase increased apparently, and the cells in S phase decreased significantly (PPConclusion: Modified Maimendong Tang combined with cisplatin can inhibit the proliferation, invasion and metastasis and induce the apoptosis of lung cancer cells. Modified Maimendong Tang can synergistically enhance the action of cisplatin. The mechanism may be related to the down-regulation of Caspase-3 and EGFR protein expressions.

The mechanism of Annexin A1 regulating the proliferation, apoptosis and migration of bladder cancer cells / 中华泌尿外科杂志

Objective@#Explore the function and regulatory mechanism of Annexin A1 (ANXA1) in bladder cancer cell proliferation, apoptosis and migration.@*Methods@#From February 2018 to June 2019, we use T24 cells as the model and divide it into over-expression control group (ctrl), ANXA1 over-expression group (ANXA1), knockdown control group (shctrl), ANXA1 knockdown group 1 (shANXA1-1), ANXA1 knockdown group 2 (shANXA1-2) and ANXA1 knockdown group 3 (shANXA1-3). 24 hours after the culture, the cells were collected and the mRNA expression level of ANXA1 was detected by Real-Time quantitative PCR. The cell activity was detected by CCK-8; the cell apoptosis and cycle were detected by flow cytometry. The cell migration was detected by Transwell assay.@*Results@#The Real-Time quantitative PCR showed that the expression of ANXA1 in the over expression group was significantly higher than that in the over expression control group (15 369.00±874.20 and 1.00±0.07, P<0.001). The expression of ANXA1 in the knockdown group 2 and 3 were significantly lower than that in the knockdown control group (0.51±0.04, 0.51±0.02 and 1.00±0.04, P<0.001). Compared with the over expression control group(1.61±0.01), the cell activity of the over expression group(2.04±0.02)was significantly increased (P<0.001), while the activity of the knockdown group 2 and 3 (1.40±0.002 and 1.31±0.003)were significantly decreased than the knockdown ctrl group (1.73±0.01)(P<0.001). The results of flow cytometry showed that the number of G0/G1 cells in the over-expression group was significantly lower than that in the over-expression control group (28.14±0.33 and 46.19±0.73, P<0.001), while that in the knockdown group 2 and 3 were significantly higher than that in the knockdown control group (58.670±0.49, 62.34±4.01 and 45.59± 0.19, P<0.001 and P<0.05). There was no significant difference in the number of apoptosis between the over-expression group and the over-expression control group (P>0.05), while the number of apoptosis in the knockdown group 2 and 3 were significantly higher than that in the knockdown control group (13.04%, 14.58% and 7.76%, P<0.001). Cell function analysis showed that the number of cells passing through the membrane of the over expression group was significantly higher than that of the over expression group (525.00±9.30 and 385.70±13.40, P<0.01), while that of the knockdown group 2 and 3 were significantly lower than that of the knockdown control group (214.70±6.40, 226.00±5.30 and 398.70±10.00, P<0.001).@*Conclusions@#Over-expression of ANXA1 significantly promoted the proliferation, cycle and migration of T24 cells and inhibited apoptosis. On the contrary, ANXA1 knockdown inhibited the proliferation, cycle and migration of T24 cells and promoted apoptosis.