scholarly journals Upregulation of MDR- and EMT-Related Molecules in Cisplatin-Resistant Human Oral Squamous Cell Carcinoma Cell Lines

2019 ◽  
Vol 20 (12) ◽  
pp. 3034 ◽  
Author(s):  
Hyeong Sim Choi ◽  
Young-Kyun Kim ◽  
Pil-Young Yun
Keyword(s):  
Drug Resistance ◽  
Squamous Cell Carcinoma ◽  
Multidrug Resistance ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Western Blotting ◽  
Acquired Drug Resistance ◽  
Established Cell Lines ◽  
Established Cell

Cisplatin is one of the major drugs used in oral cancer treatments, but its usage can be limited by acquired drug resistance. In this study, we established three cisplatin-resistant oral squamous cell carcinoma (OSCC) cell lines and characterized them using cell viability assays, qPCR, Western blotting, FACS, immunofluorescence, and wound healing assays. Three OSCC cell lines (YD-8, YD-9, and YD-38) underwent long-term exposure to cisplatin, eventually acquiring resistance to the drug, which was confirmed by an MTT assay. In these three newly established cell lines (YD-8/CIS, YD-9/CIS, and YD-38/CIS), overexpression of multidrug resistance (MDR)-related genes was detected by qPCR and Western blotting. The cell lines displayed an increase in the functional activities of breast cancer resistance protein (BCRP) and multidrug resistance protein1 (MDR1) by rhodamine 123 and bodipy FL prazosin accumulation assays. Moreover, the cisplatin-resistant cells underwent morphological changes, from round to spindle-shaped, increased expression of epithelial-to-mesenchymal transition (EMT)-related molecules such as N-cadherin, and showed increased cell migration when compared with the parental cell lines. These results suggest that these newly established cell lines have acquired drug resistance and EMT induction.

scholarly journals LncRNA HOXA11-AS Promotes Proliferation and Cisplatin Resistance of Oral Squamous Cell Carcinoma by Suppression of miR-214-3p Expression

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Xiaoyan Wang ◽  
Hong Li ◽  
Jing Shi
Keyword(s):  
Drug Resistance ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Squamous Cell ◽  
Loss Of Function ◽  
Downstream Target ◽  
Xenograft Mice ◽  
Resistant Cells

Drug resistance to platinum limited therapeutic options for oral squamous cell carcinoma (OSCC). In the current study, we investigated the role of lncRNA HOMEOBOX A11 (HOXA11) antisense RNA (HOXA11-AS) in OSCC resistance to cisplatin (CDDP). We used clinical tissues and OSCC cell lines and induced CDDP resistance in OSCC cells. Gain and loss of function were performed in OSCC-resistant cells. Xenograft mice were also established. HOXA11-AS expression was increased in OSCC clinical tissues and cell lines and upregulated in CDDP-resistant cells. Upregulation of HOXA11-AS promoted proliferation in CDDP-sensitive cells and inhibited CDDP-induced cytotoxicity. In contrast, downregulation of HOXA11-AS decreased proliferation in CDDP-resistant cells and increased CDDP-induced cytotoxicity. Knockdown of HOXA11-AS inhibited the tumor growth in xenograft mice injected by CDDP. Downregulation of HOXA11-AS increased apoptosis and caspase 3 activities in CDDP-resistant OSCC cells. Bioinformatics, reporter assay, and loss and gain of function assay indicated that HOXA11-AS and miR-214-3p could negatively regulate each other. miR-214-3p was decreased in OSCC clinical tissues and cell lines. We further revealed that proto-oncogene serine/threonine-protein kinase (PIM1) was the target of miR-214-3p. PIM1 expression could be negatively regulated by miR-214-3p and positively regulated by HOXA11-AS. Inhibition of PIM1 suppressed anti-miR-214-3p-induced increase of cell proliferation and decrease of apoptosis. In summary, HOXA11-AS was identified to facilitate CDDP-resistance in OSCC and miR-214-3p/PIM1 was found to be the downstream target of HOXA11-AS. The findings highlight the importance of HOXA11-AS/miR-214-3p/PIM1 axis in the drug resistance of OSCC and provide potential targets for improving chemotherapy of OSCC.

scholarly journals Increased FOXM1 Expression by Cisplatin Inhibits Paclitaxel-Related Apoptosis in Cisplatin-Resistant Human Oral Squamous Cell Carcinoma (OSCC) Cell Lines

2020 ◽  
Vol 21 (23) ◽  
pp. 8897
Author(s):  
Hyeong Sim Choi ◽  
Young-Kyun Kim ◽  
Kyung-Gyun Hwang ◽  
Pil-Young Yun
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Squamous Cell ◽  
Resistant Cell ◽  
Antagonistic Effect ◽  
Acquired Drug Resistance ◽  
Foxm1 Expression ◽  
Induced Apoptosis

Cisplatin and paclitaxel are commonly used to treat oral cancer, but their use is often limited because of acquired drug resistance. Here, we tested the effects of combined cisplatin and paclitaxel on three parental (YD-8, YD-9, and YD-38) and three cisplatin-resistant (YD-8/CIS, YD-9/CIS, and YD-38/CIS) oral squamous cell carcinoma (OSCC) cell lines using cell proliferation assays and combination index analysis. We detected forkhead box protein M1 (FOXM1) mRNA and protein expression via real-time qPCR and Western blot assays. Cell death of the cisplatin-resistant cell lines in response to these drugs with or without a FOXM1 inhibitor (forkhead domain inhibitory compound 6) was then measured by propidium iodide staining and TdT dUTP nick end labeling (TUNEL) assays. In all six OSCC cell lines, cell growth was more inhibited by paclitaxel alone than combination therapy. Cisplatin-induced overexpression of FOXM1 showed the same trend only in cisplatin-resistant cell lines, indicating that it was associated with inhibition of paclitaxel-related apoptosis. In summary, these results suggest that, in three cisplatin-resistant cell lines, the combination of cisplatin and paclitaxel had an antagonistic effect, likely because cisplatin blocks paclitaxel-induced apoptosis. Cisplatin-induced FOXM1 overexpression may explain the failure of this combination.

scholarly journals Identification of E2F transcription factor 7 as a novel potential biomarker for oral squamous cell carcinoma

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Ping Zhou ◽  
Lei Xiao ◽  
Xiaonan Xu
Keyword(s):  
Squamous Cell Carcinoma ◽  
Transcription Factor ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Squamous Cell ◽  
Loss Function ◽  
High Expression ◽  
E2f Transcription Factor ◽  
Gain And Loss

Abstract Background As a tumor-accelerating transcriptional factor, E2F transcription factor 7 (E2F7) was up-regulated in many forms of cancers. Nevertheless, little has been reported about the impacts of E2F7 on oral squamous cell carcinoma (OSCC). Here, we aimed to probe whether E2F7 had influences on OSCC and its potential mechanism. Methods The expression of E2F7 in OSCC tissues was analyzed using the data acquired from TCGA and ONCOMINE databases. E2F7 prognostic value in OSCC patients was analyzed utilizing TCGA database. The expression of E2F7 in OSCC cell lines was detected by qRT-PCR. Gain-and loss-function of E2F7 assays in TCA-83 and CAL27 cells were performed respectively to inquire the function of E2F7. Western blotting was applied to test the alternations of EMT-related markers. Results In OSCC tissues, E2F7 was highly expressed. Besides, high expression of E2F7 predicted worse prognosis in OSCC patients. Moreover, E2F7 was over-expressed in TCA-83, HSC-4 and CAL27 (all OSCC cell lines) cells relative to that in HNOK (a normal cell line) cells. Gain-and loss-function assays displayed that deficiency of E2F7 suppresses CAL27 cell growth, migration, invasion and E2F7 high-expression resulted in inverse outcomes in TCA-83 cells. Finally, we found that silencing of E2F7 facilitated E-cadherin protein expression level and reduced N-cadherin, Vimentin and Snail protein levels in CAL27 cells, whilst E2F7 high-expression exhibited the opposite effects in TCA-83 cells. Conclusions These outcomes indicated that E2F7 performs a carcinogenic role in OSCC, which provides a theoretical basis for the therapeutic strategies of OSCC.

scholarly journals Evaluation of Hyaluronic Acid to Modulate Oral Squamous Cell Carcinoma Growth In Vitro

2020 ◽  
Vol 11 (4) ◽  
pp. 72
Author(s):  
Jordan Ringer ◽  
Bryan Morrison ◽  
Karl Kingsley
Keyword(s):  
Growth Rate ◽  
Squamous Cell Carcinoma ◽  
Hyaluronic Acid ◽  
Oral Squamous Cell Carcinoma ◽  
Tumor Growth ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Squamous Cell ◽  
Chemotherapeutic Agents ◽  
Oral Tumor

Introduction: Previous studies have demonstrated that glycosaminoglycan hyaluronic acid (HA) is capable of mediating oral tumor growth. Some clinical evidence has suggested reduced HA expression predicts poor cancer prognosis and that HA-chemotherapy conjugates may function synergistically to inhibit oral tumor growth. Other studies have found conflicting results that suggest enhanced CD44-HA-mediated growth and proliferation. Due to the lack of clarity regarding HA function, the primary goal of this study was to investigate the effects of HA using well-characterized oral cancer cell lines. Methods: Using several commercially available oral squamous cell carcinoma lines (and a normal non-cancerous control), 96-well growth and viability assays were conducted using HA (alone and in combination with chemotherapeutic agents paclitaxel and PD98059). Results: Different results were observed in each of the cell lines evaluated. HA induced small, non-significant changes in cellular viability among each of the cell lines within a narrow range (1–8%), p = 0.207. However, HA induced differing effects on growth, with minimal, non-significant changes among some cell lines, such as SCC4 (+1.7%), CCL-30 (−2.8%), and SCC15 (−2.5%), p = 0.211 and more robust inhibition among other cell lines, SCC9 (−24.4%), SCC25 (−36.6%), and CAL27 (−47.8%), p = 0.0001. Differing effects were also observed with growth and viability under concomitant administration of HA with PD98059 or paclitaxel. Further analysis of these data revealed strong inverse (Pearson’s) correlations between initial baseline growth rate and responsiveness to HA administration, ranging from R = −0.27 to R = −0.883. Conclusion: The results of this study revealed differing responses to HA, which may be inversely correlated with intrinsic characteristics, such as the baseline growth rate. This may suggest that the more rapidly growing cell lines are more responsive to combination therapy with hyaluronic acid; an important finding that may provide insights into the mechanisms responsible for these observations.

scholarly journals Genetically-defined novel oral squamous cell carcinoma cell lines for the development of molecular therapies

Oncotarget ◽  
2016 ◽  
Vol 7 (19) ◽  
pp. 27802-27818 ◽  
Author(s):  
Muhammad Zaki Hidayatullah Fadlullah ◽  
Ivy Kim-Ni Chiang ◽  
Kalen R. Dionne ◽  
Pei San Yee ◽  
Chai Phei Gan ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Squamous Cell ◽  
Carcinoma Cell ◽  
Squamous Cell Carcinoma Cell ◽  
Carcinoma Cell Lines ◽  
Molecular Therapies

scholarly journals Reduction of Intracellular-Reactive Oxygen Species and Diminished Mitogen-Activated Protein Kinases (MAPKs) Activation are Associated with Oral Squamous Cell Carcinoma Cell Aggressiveness

2017 ◽  
Vol 15 (2) ◽  
pp. 131-141
Author(s):  
Tanyarath UTAIPAN ◽  
Apsorn SATTAYAKHOM ◽  
Issara PRACHONGSAI ◽  
Nurdina CHARONG ◽  
Warangkana CHUNGLOK
Keyword(s):  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Protein Kinases ◽  
Cell Lines ◽  
Oxygen Species ◽  
Mitogen Activated Protein Kinases ◽  
Mitogen Activated Protein

Oral squamous cell carcinoma (OSCC) is a serious health problem in many countries. Several drugs have been used to treat head and neck and oral cavity cancers. However, the success rate has not been impressive because of the heterogeneity of cancerous cells, resulting in differential responsiveness to chemotherapy. Two distinct phenotypes of OSCC cells, the CLS-354/WT and CLS-354/DXcells, have been used as in vitro cell models for this study. CLS-354/DXcells were more aggressive than CLS-354/WTcells, supported by the observation that CLS-354/DXcells can undergo epithelial-mesenchymal transition (EMT), grow anchorage-independently, and increase invasiveness. We investigated the preliminary redox status of these 2 cell lines, including levels of reactive oxygen species (ROS) and cellular antioxidants, using flow cytometry analysis and ABTS+ free radical scavenging assay, respectively. A 7-fold decrease in ROS level was detected in CLS-354/DXcells, comparing with CLS-354/WTcells, while antioxidant capacity was not different from that of CLS-354/WT cells. Hydrogen peroxide, a ROS modulating agent, could induce ROS levels, and caused cell death in CLS-354/WT greater than that of CLS-354/DX cells. Of note, hydrogen peroxide-induced cytotoxicity could be rescued by N-acetyl cysteine, confirming ROS-mediated cytotoxicity in both cell lines. ROS-sensitive mitogen-activated protein kinases (MAPKs) were observed using immunoblot assay. The expressions of p-JNK1/2 and p-p38 MAPK in CLS-354/DX cells were absent, while these expressions were abundantly detected in CLS-354/WTcells. This suggests that lower ROS levels, with the concomitant reduction of JNK and p38 MAPK activation in CLS-354/DX cells, are associated with cancer cell aggressiveness. These findings provide significant evidence of the resistance to ROS-modulating agents in aggressive OSCC cells.

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