Antisense oligonucleotide p45Skp-2 suppresses migratory chemotactic and metastasis of oral malignant Burkitt’s lymphoma cell through down-regulation of MTA-1 and induction of E-cadherin mechanism (original) (raw)
Related papers
2020
Burkitt’s lymphoma (BL) is an uncommon type of Non-Hodgkin lymphoma (NHL). It is a highly aggressive type of B-cell lymphoma and the most common childhood cancer. Treatment for this cancer is still limited. However, a new strategy for refractory tumor, gene therapy is watched with keen interest. The aim of study was to investigate the expression of non-metastatic 23 (nm-23) and metastatic associated protein-1 (MTA-1) of an oral malignant Burkitt’s lymphoma induced by oligonucleotide p27 sense (p27 S). The true experimental study with post-test only control group design was confirmed in this study. For detection of nm-23, MTA-1, p27Kip-1 and tubulin protein expressions were carried-out by Western blotting analysis. Induction of apoptosis was analyzed by double staining using acridine orange-ethidium bromide (AO-EB). Results revealed the expression of nm-23 and p27Kip-1 protein was markedly increased in cell transfected with p27 sense. Contrally, down regulation of MTA-1 protein was ...
2020
Oral cancer cells (TYS) and the signalling pathways involved in metastasis, in response to cancer-associated fibroblasts (CAFs, COM) and normal oral mucosal fibroblasts (MM1) was studied. Metastatic cell behaviour was observed by cell-scatter, 3D-collagen gel migration and 3D-spheroid invasion assays. Akt, MAPK, EGFR, TGFβRii and CXCR4 inhibitors were used to identify the signalling pathways involved. Signalling pathway protein expression and activation were assessed by SDS-PAGE and Western Blotting. COM-CM (conditioned medium) and MM1-CM stimulated cancer cell scattering, which was blocked only by the Akt inhibitor. COM-CM induced scattered cancer cells showed higher levels of Akt phosphorylation than the negative control and MM1-CM. Migration and invasion of TYS cells into the collagen gels from the spheroids was stimulated by CM from both sources, compared to the negative control. COM cells stimulated TYS, cancer cell invasion into the collagen more than MM1 and the control. Akt ...
Clinica Chimica Acta, 2010
Background: The role of bcl-2 expression, bcl-2 inhibitor HA14-1, and matrix metalloproteinase (MMP)-2 is still unclear in nasopharyngeal carcinoma (NPC). Methods: From 1996 to 2000, 145 patients with newly diagnosed NPC who were treated with high dose radiotherapy were enrolled. The relationship between bcl-2 expression, TNM stage, and disease-specific survival was analyzed. Furthermore, the NPC cell line HONE-1 was used to confirm the relationship between bcl-2 and cell metastasis. Results: Among the 145 patients, 47 (32.4%) of them were bcl-2 positive. The expression of bcl-2 was significantly correlated with neck lymph node metastasis (p = 0.006), and patients with negative bcl-2 expression had better disease-free survival (p = 0.007). A Cox regression model revealed that only bcl-2 expression (p = 0.023) and stage IV (p = 0.043) were statistically significant in the prognosis of NPC. In vitro analysis also showed that treatment with the bcl-2 inhibitor HA14-1 exerted an inhibitory effect on migration and expression of MMP-2 in HONE-1 cells. Conclusions: Bcl-2 expression represents an important and easily assayed prognostic factor, and it may play an important role in lymph node metastasis. Inhibition of the migration mediated by MMP-2 may be a key feature for the prevention of cancer metastasis.
The anti-metastasis effects of oroxylin-a on oral squamous cell carcinoma cells
Proceedings for Annual Meeting of The Japanese Pharmacological Society, 2019
Oral cancer ranks the seventh in cancer-related deaths in men and also the thirteenth most common in women worldwide. The lymph node and distant metastasis are the major causes of death in oral cancer patients. Therefore, it is a critical need to identify new potential therapeutic agents against oral cancer metastasis. Oroxylin A (oro-A), a main bioactive flavonoid extracted from Scutellaria radix, has been reported to inhibit migration in various human cancers. Our previous study demonstrated that a long-term exposure to oro-A further suppress cell migration significantly than short-term oro-A exposure and without cytotoxicity on oral cancer cells treatment. Hence, we aimed to find out the anti-migration effects and underlying mechanisms of long-term oro-A exposure on oral cancer cells. In present study, we found that the migration abilities of the oral cancer cells long-term oro-A treatment may increased by chemokine ligand 2 (CCL2). It seems that CCL2 plays a critical role in anti-migration of long-term oro-A exposure. The CCL2 treatment was demonstrated to activate the protein levels of the pERK , p-JNK, NF-κB, MMP-2&9 signaling pathway. We also found that oro-A inhibit the metastasis via suppressing the expression of CCL2 in vivo. Our results indicate long term exposure to oro-A inhibits migration in human oral cancer cells through CCL2/ERK/NF-κB/MMP-2,9 signaling pathway.
International Journal of Molecular Sciences, 2018
NVP-BEZ235 or BEZ235 is a dual inhibitor of adenosine triphosphate (ATP)-competitive phosphoinositide 3-kinase (PI3K)/mammalian-target-of-rapamycin (mTOR) and is promising for cancer treatment. Because it targets more than one downstream effector, a dual approach is promising for cancer treatment. The aim of this study was to evaluate the efficacy of NVP-BEZ235 in treating oral cavity squamous cell carcinoma (OSCC). Two human OSCC cell lines, SCC-4 and SCC-25, were used in this study. PI3K-AKT signaling, proliferation, and cell migratory and invasion capabilities of OSCC cells were examined. In NVP-BEZ235-treated SCC-4 and SCC-25 cells, the phosphorylation of 70-kDa ribosomal S6 kinase (p70S6K), but not mTOR, decreased within 24 h. NVP-BEZ235 inhibited OSCC-cell proliferation, migration, and invasion possibly by directly deregulating the phosphorylation of p70S6K. The phospho-p70S6K inhibitor mimicked the effects of NVP-BEZ235 for preventing proliferation and weakening the migratory...
2001
The protein kinase C (PKC) is a family of serine/threonine kinases that are key regulatory enzymes involved in growth, differentiation, cytoskeletal reorganization, tumor promotion, and migration. We investigated the functional involvement of PKC isotypes and of E-cadherin in the regulation of the locomotion of six human colon-adenocarcinoma cell lines. The different levels of the PKC ␣ and the E-cadherin expression have predictable implications in the spontaneous locomotory activity. With the use of PKC ␣-specific inhibitors (safingol, Go6976) as well as the PKC ␦-specific inhibitor rottlerin, we showed that only PKC ␣ plays a major role in the regulation of tumor cell migration. The results were verified by knocking out the translation of PKC isozymes with the use of an antisense oligonucleotide strategy. After stimulation with phorbol ester we observed a translocation and a colocalization of the activated PKC ␣ at the plasma membrane to the surrounding extracellular matrix. Furthermore, we investigated the functional involvement of E-cadherin in the locomotion with the use of a blocking antibody. A high level of PKC ␣ expression together with a low E-cadherin expression was strongly related to a high migratory activity of the colon carcinoma cells. This correlation was independent of the differentiation grade of the tumor cell lines.
Differential inhibition of single and cluster type tumor cell migration
Anticancer research, 2009
For the control of tumor metastasis it is important to identify chemical compounds with antimigratory potency. Agents acting against single cell and cluster type migration are necessary for successful antimetastatic therapy. In the present study, the migration of HT-1080 fibrosarcoma cells and OSCORT osteosarcoma cells was compared in a Boyden chamber and in an extracellular matrix (ECM)-based three-dimensional cell culture (3-DCC) model system. The Boyden chamber offers a model of single tumor cell migration, whereas the 3-DCC model system demonstrates invasive growth in the form of a cluster. Since PD98059 (MEK inhibitor) exclusively reduced migration in the 3-DCC model, it may be plausible that the ERK/MAPK signaling pathway is essential for cluster type migration. Interestingly, single cell migration was stimulated upon blocking phosphatidylinositol 3-kinase (PI3K) and also p38-MAPK by treatment with LY294002 and SB203580 respectively. A remarkable reduction of single cell migra...
Clinical & Experimental Metastasis, 2020
We explored the role of the transcription factor, NF-κB, and its upstream kinase IKKβ in regulation of migration, invasion, and metastasis of cisplatin-resistant head and neck squamous cell carcinoma (HNSCC). We showed that cisplatin-resistant HNSCC cells have a stronger ability to migrate and invade, as well as display higher IKKβ/NF-κB activity compared to their parental partners. Importantly, we found that knockdown of IKKβ, but not NF-κB, dramatically impaired cell migration and invasion in these cells. Consistent with this, the IKKβ inhibitor, CmpdA, also inhibited cell migration and invasion. Previous studies have already shown that N-Cadherin, an epithelial-mesenchymal transition (EMT) marker, and IL-6, a pro-inflammatory cytokine, play important roles in regulation of HNSCC migration, invasion, and metastasis. We found that cisplatin-resistant HNSCC expressed higher levels of N-Cadherin and IL-6, which were significantly inhibited by CmpdA. More importantly, we showed that CmpdA treatment dramatically abated cisplatin-resistant HNSCC cell metastasis to lungs in a mouse model. Our data demonstrated the crucial role of IKKβ in control of migration, invasion, and metastasis, and implicated that targeting IKKβ may be a potential therapy for cisplatin-resistant metastatic HNSCC.
Effects of cisplatin on matrix metalloproteinase-2 in transformed thyroid cells
Biochemical Pharmacology, 2010
We investigated the effects of cisplatin (cisPt) on matrix metalloproteinase-2 (MMP-2) gelatinolitic activity in transformed PC E1Araf rat thyroid cells. Cells incubated with increasing cisPt concentrations showed dose-and time-dependent decrease of the MMP-2 protein and activity. CisPt provoked the translocation from the cytosol to the plasma membrane of atypical protein kinase C-zeta (PKC-δ) and the activation of PKB/AKT. The effect of cisPt on MMP-2 was dependent on PKC-δ activation since it was potentiated by a myristoylated PKC-δ pseudo substrate peptide or by PKC-δ down regulation by siRNA. Moreover, MMP-2 activity modulation by cisPt was also dependent on PKB/AKT activation since it was decreased by PKB/AKT down regulation by siRNA or by pharmacological inhibition of PI3K, thus indicating the importance of the balance of PKB/AKT and PKC-δ in regulating the cisPt effect on MMP-2 activity. The PC E1Araf cells displayed a migratory capacity that was blocked by MMP-2 down regulation using siRNA or pharmacological inhibition. The inhibition of cell migration was also obtained with cisPt; in cisPt-treated cells the administration of MMP-2 active protein was able to restore cell migration capacity. In conclusion, the decrease of MMP-2 secretion after cisPt was allowed by PKB/AKT and counteracted by PKC-δ; the cisPt-provoked inhibition of MMP-2 secretion ended in reduction of cell migration.