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1.
Article | IMSEAR | ID: sea-210498

ABSTRACT

Drug resistance is a major inconvenience which lowers the traditional chemotherapeutic efficacy and is a highly undesirable therapeutic problem which poses particular challenges in the case of colorectal cancer. Fucoxanthin is a natural orange-carotenoid, predominantly found in edible brown algae and justifiably considered as a nutritional ingredient with the capacity to powerfully enhance concurrent drug chemotherapy. It has been well-documented that fucoxanthin has good potential for anti-cancer activity while offering a remarkable range of biological activities. Accordingly, it has gained prominence in the research field as interest grows in the molecular mechanism which is associated with cancer therapy. This study was undertaken to assess the anti-cancer activity and to explore the molecular mechanism of fucoxanthin on the inhibition of cell proliferation, cell adhesion, and cell invasion, in addition to determining the synergistic effect of drug-drug combinative treatment in colorectal cancer cells. SW-620 cells were cultivated with fucoxanthin for 24, 48, 72, and 96 hours with co-treatment by 5-FU to evaluate the synergistic potential. The cell viability of cancerous cells was determined by MTT colorimetric assay. The inhibitory effects of cell invasion and adhesion were measured in the presence of fucoxanthin with 5-FU in various concentrations to determine MMP-9 gene and protein expression after treatment of the cells by RT-PCR and ELISA assay. The results illustrated that fucoxanthin profoundly inhibited cell proliferation of SW-620 cells, accompanied by arrested growth and diminished invasive ability, which was mediated at least in part by the down-regulation of MMP-9, mRNA, and protein expression. In particular, fucoxanthin strongly attenuated the anti-proliferative effect of established 5-FU by modulating the habitual hallmark of cancerous cells. These results illustrate the capacity of fucoxanthin to eradicate cancer cells and indicate the possibility that fucoxanthin could serve as a promising natural marine product derived from seaweed. The critical data in our studies will serve as the preliminary results for further studies of marine drugs in both experimental models and well-controlled clinical trials

2.
Article in English | WPRIM | ID: wpr-825867

ABSTRACT

Objective:To investigate the cytotoxic, apoptotic and inhibitory activities on cell migration and invasion of plumbagin in the human cholangiocarcinoma (CCA) cell line (CL-6) in comparison with human embryonic fibroblast cell line (OUMS).Methods:Cytotoxicity activity was evaluated using MTT assay. Inhibitory effect on cell migration and invasion were investigated using label-free real-time cell analysis and QCM ECMatrix cell invasion chamber, respectively. Apoptotic activity was evaluated using flow cytometry and CellEvent™ Caspase 3/7 assay.Results:Based on results of the cytotoxicity test in CL-6 cells, 50% inhibitory concentration (ICConclusions:The cytotoxic activity and inhibition of migration and invasion including apoptosis induction in the human CCA cell line (CL-6) suggest that plumbagin could be a promising candidate for CCA chemotherapeutics. However, its relatively low selective cytotoxic effect on CCA cells is a major concern.

3.
Article in Chinese | WPRIM | ID: wpr-608187

ABSTRACT

Objective To investigate the biological effects of exosomes secreted by KYSE410 cells on migration and invasion of KYSE410,KYSE510,YES2 cells and the possible mechanisms underlying the phenotype change.Methods The exosomes were isolated from the conditional supernatant of esophageal cancer cell line KYSE410 by ultracentrifugation.The morphology of exosomes was observed by transmission electron microscopy (TEM).Western blotting was used to detect the protein markers of exosomes.The uptaken of fluorescence-labeled KYSE410 exosomes by KYSE410,KYSE510 and YES2 was also recorded under confocal microscopy.Migration and invasion ability of the three esophageal carcinoma cell lines and the effects of exosomes from KYSE410 on migration and invasion of KYSE410,KYSE510 and YES2 cells were analyzed by Transwell chamber,respectively.The alteration of Wnt/β-catenin and PI3K/Akt pathway-related proteins were detected by Western blotting.Results The membrane structure of KYSE410 derived exosomes could be observed with its diameter ranged between 30-100nm.The invasion and migration ability of three esophageal cancer cells are KYSE410> KYSE510> YES2.KYSE410 exosomes promoted the migration and invasion of KYSE410,KYSE510 and YES2 cells.Conclusions Concentrated exosomes derived from the highly migratory and invasive esophageal cancer cell line KYSE410 promoted the migration and invasion potentials of itself and esophageal cancer cell lines KYSE510 and YES2,which possibly exerted the effects by activating Wnt/β-catenin and PI3K/Akt signaling pathways.

4.
Article in Chinese | WPRIM | ID: wpr-275469

ABSTRACT

This study aimed to analyze the analgesic effect and related central mechanisms of CQ prescription on cancer invasion induced mirror image pain (CIIMIP)in model mice.In the study, male BALB/c mice were randomly divided into normal group, operation control group (injected with 0.2 mL inactivated S180 sarcoma cell sap), model group (injected with 0.2 mL S180 sarcoma cell sap on the right leg near the greater trochanter of femur) and CQ prescription low dose group (intraperitoneally injected with CQ prescription 100 mg•kg⁻¹ on the basis of model mice), CQ prescription middle dose group (intraperitoneally injected with CQ prescription 150 mg•kg⁻¹ on the basis of model mice), and CQ prescription high dose group (intraperitoneally injected with CQ prescription 200 mg•kg⁻¹ on the basis of model mice). Mechanical withdraw threshold (MWT) of the mirror image lateral hind paws were evaluated by Von Frey hairs before modeling and after surgery. The levels of glutamate (Glu), gamma aminobutyric acid (GABA), glycine (Gly), and taurine (Tau) in the L3-L5 spinal cord were measured by the high performance liquid chromatography-fluorescence detector (HPLC-FLD); AimPlex detection technology with multiple factors was used to detect the levels of regulated on activation in normal T-cell expressed and secreted (RANTES), monocyte chemoattractant protein (MCP-3) in the L3-L5 spinal cord. Then we observed the influence of GABAa receptor antagonist (Bicuculline) on analgesic effect of CQ prescription.The results indicated that CQ prescription could remarkably increase MWT of model mice(P<0.01, P<0.05), decrease the level of Glu(P<0.01, P<0.05), improve the levels of GABA, Gly, Tau(P<0.01, P<0.05), lower the ratio of Glu/GABA(P<0.01, P<0.05), and reduce the levels of RANTES, MCP-3(P<0.05) in the L3-L5 spinal cord, and GABAa receptor antagonist significantly blocked the analgesic effect of CQ prescription at two time points(P<0.05).This study showed that CQ prescription had significant analgesic effect on CIIMIP model mice, and its mechanism was associated with regulating the balance between excitability amino acid(EAA) and inhibitory amino acid (IAA) transmitters in central nervous system, partially activating GABAa receptor, and reducing the release of RANTES and MCP-3 in the spinal cord.

5.
Article in Chinese | WPRIM | ID: wpr-465202

ABSTRACT

Objective To study the roles of neurochemicals as Glu, GABA in the spinal cord and SP, DynA1-13 in the cerebral cortex of mirror image pain in cancer invasion pain model and the effects of gabapentin on them.Methods Male BALB/c mices were randomly divided into native group, sham group (injected inactivated S180 sarcoma cell sap), model group (injected 0.2 mL of S180 sarcoma cell sap on the right leg near the greater trochanter of femur) and GBP group (intraperitoneally injected gabapentin 120 mg/kg on the basis of model mice).Mechanical withdraw threshold of the ipsilateral and contralateral hind paw were evaluated by Von Frey hairs before and after surgery.The levels of Glu and GABA in the L3-L5 spinal cord were measured by the high performance liquid chromatography-fluorescence detector ( HPLC-FLD ) and radioimmunoassay was used to detect the concentrations of SP and DynA1-13 in the cerebral cortex.Results The mechanical withdraw threshold of contralateral mirror sites in model mice appeared same trend and approximate degree of decline, following the generation of cancer invasion pain of ipsilateral hind paw.Compared with native group, the concentrations of Glu in the spinal cord and SP in the cerebral cortex in model group were significantly increased (P<0.05, P<0.01), and the levels of GABA in the spinal cord and Dyn A1-13 in the cerebral cortex in model group were significantly decreased (P<0.05, P<0.01).Gabapentin could significantly increase the bilateral mechanical withdraw threshold of model mice and the analgesic effect could maintain to 240 min after administration (P<0.05 or P<0.01).Moreover, gabapentin could reverse the changes of above neurochemicals in the central nervous system of mirror image pain in cancer invasion pain model mice (P<0.01 or P<0.05).Conclusion The mirror image pain phenomenon does exist in the cancer invasion pain model mice induced by S180 sarcoma.The mechanism of mirror image pain occurr and preserve in cancer invasion pain model may involve the changes of Glu, GABA in the spinal cord and SP, Dyn A1-13 in the cerebral cortex, through which gabapentin can relieve mirror image pain in cancer invasion pain model.

6.
Article in English | WPRIM | ID: wpr-362758

ABSTRACT

Intrinsic or acquired resistance to cisplatin (CDDP) is a problem for its use in cancer chemotherapy. This resistance has been reported to correlate with expression of the human copper transporter 1 and two copper export pumps, ATP7A and ATP7B. In the current study, we investigated the correlation between the expression of these transporters and sensitivity to CDDP using four cell lines derived from each of high invasive oral squamous cell carcinoma (OSCC) and low invasive OSCC. We found that the amount of CDDP accumulated in high invasive OSCC cell lines (Yamamoto-Kohama criteria: grade 4C and 4D) with strong intrinsic tolerance was lower than in low invasive OSCC cell lines (grade 3) with weak intrinsic tolerance. Additionally, overexpression of ATP7B mRNA in cell lines derived from high invasive OSCC conferred low sensitivity to CDDP. Furthermore, the accumulation and sensitivity of CDDP was higher in HOC313 cells transfected with the ATP7B siRNA than in cells transfected with the nonsense siRNA. These results suggest that the overexpression of ATP7B results in the export of and, therefore, resistance to CDDP. Furthermore, ATP7B may be a key determinant of the intrinsic resistance to CDDP.

7.
Article in English | WPRIM | ID: wpr-13850

ABSTRACT

CD63, which belongs to the tetraspanin membrane proteins, has been proposed to play an important role in inhibiting melanoma metastasis. To determine whether reduction of CD63 expression, which frequently occurs in the malignant progression of human melanoma, is responsible for metastasis promotion, we transfected the antisense CD63 cDNA into MelJuso melanoma cells having endogenous CD63 expression. The antisense CD63 transfectant clones showing decreased CD63 expression displayed increased cell motility, matrix-degrading activity, and invasiveness in vitro when compared with the control transfectant cells. The antisense CD63 cDNA-transfected cells also exhibited altered adhesiveness to extracellular matrix. The results suggest that reduced CD63 expression contributes to the invasive and metastatic ability of human melanoma cells.


Subject(s)
Antigens, CD/biosynthesis , Gene Expression Regulation, Neoplastic , Humans , Melanoma/genetics , Neoplasm Invasiveness/genetics , Platelet Membrane Glycoproteins/biosynthesis , Reverse Transcriptase Polymerase Chain Reaction
8.
Article in Korean | WPRIM | ID: wpr-54343

ABSTRACT

The gastric carcinoma shows various molecular and genetic alterations in its development and progression. There are evidences that the changes of the expression of cell adhesion molecules affect the morphogenesis of the tumor as well as the tumor progression and metastasis. The purpose of this study is the evaluation of the expression pattern of a cell adhesion molecule, E-cadherin, and a tumor suppression gene, p53, by immunohistochemical stain and the relationship of their expressions with clinicopathologic findings in gastric adenocarcinoma tissue. The E-cadherin expression was absent or reduced in 93 cases (73.2%) and p53 was positive in 98 cases (77.2%) of 127 gastric adenocarcinomas. The frequency of reduced E-cadherin expression was significantly higher in poorly differentiated adenocarcinomas (p=0.04) and in diffuse type (p=0.01), but that of p53 positivity was not significantly correlated with tumor differentiation. Both proteins showed no correlation with depth of invasion, lymph node and distant metastasis, and tumor stage. There was no correlation between E-cadherin and p53 expression. This study indicates that the altered expressions of E-cadherin and p53 are associated with the development of intestinal and diffuse types of gastric adenocarcinoma and the differentiation of the gastric adenocarcinoma is affected by cell adhesion mediated by E-cadherin, but the modes of tumor progression and metastasis are not affected by E-cadherin and p53.


Subject(s)
Adenocarcinoma , Cadherins , Cell Adhesion , Cell Adhesion Molecules , Genes, p53 , Immunohistochemistry , Lymph Nodes , Morphogenesis , Neoplasm Metastasis , Stomach Neoplasms
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