scholarly journals Plumbagin Enhances the Anticancer Efficacy of Cisplatin by Increasing Intracellular ROS in Human Tongue Squamous Cell Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-21 ◽  
Author(s):  
Danfeng Xue ◽  
Shu-Ting Pan ◽  
Xiongming Zhou ◽  
Fangfei Ye ◽  
Qun Zhou ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Side Effects ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Molecular Mechanisms ◽  
Tongue Squamous Cell Carcinoma ◽  
Human Tongue ◽  
Intracellular Ros

Cisplatin is widely used in the treatment of tongue squamous cell carcinoma (TSCC), but its clinical efficacy is limited by drug resistance and toxic side effects. Hence, a novel compound capable of enhancing the anticancer effect of cisplatin while reducing the side effects is urgently needed. We have previously shown that plumbagin (PLB), an anticancer phytochemical, is able to inhibit the growth of TSCC in vitro and in vivo. The objective of this study was to investigate the effect of PLB in reversing the resistance of TSCC to cisplatin as well as its molecular mechanisms. Here, we found that PLB enhances cisplatin-induced cytotoxicity, apoptosis, and autophagy in CAL27 and cisplatin-resistant CAL27/CDDP cells. PLB could inhibit the viability and growth of TSCC cells by increasing the production of intracellular reactive oxygen species (ROS). In addition, the combination treatment of PLB and cisplatin resulted in a synergistic inhibition of TSCC viability, apoptosis, and autophagy by increasing intracellular ROS, which may be achieved by activating JNK and inhibiting AKT/mTOR signaling pathways. Finally, the synergistic treatment was also demonstrated in vivo. Therefore, PLB combined with cisplatin is a potential therapeutic strategy against therapy TSCC cisplatin resistance.

scholarly journals The molecular mechanisms of the long noncoding RNA SBF2-AS1 in regulating the proliferation of oesophageal squamous cell carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wenjuan Zha ◽  
Xiaomin Li ◽  
Xiaowei Tie ◽  
Yao Xing ◽  
Hao Li ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Histological Grade ◽  
Oesophageal Squamous Cell Carcinoma ◽  
Lymphnode Metastasis

AbstractThe long noncoding RNASBF2-AS1 can promote the occurrence and development of many kinds of tumours, but its role in oesophageal squamous cell carcinoma (ESCC) is unknown. We found that SBF2-AS1 was up-regulated in ESCC, and its expression was positively correlated with tumor size (P = 0.0001), but was not related to gender, age, TNM stage, histological grade, and lymphnode metastasis (P > 0.05). It was further found that the higher the expression of SBF2-AS1, the lower the survival rate. COX multivariate analysis showed that the expression of SBF2-AS1 was an independent prognostic factor. Functional experiments show that inhibition of SBF2-AS1 can inhibit the proliferation of ESCC through in vivo and in vitro, and overexpression of SBF2-AS1 can promote the proliferation of ESCC and inhibit its apoptosis. In mechanism, SBF2-AS1/miR-338-3P, miR-362-3P/E2F1 axis are involved in the regulation of ESCC growth. In general, SBF2-AS1 may be used as ceRNA to combine with miR-338-3P and miR-362-3P to up-regulate the expression ofE2F1, and ultimately play a role in promoting cancer. It may be used as a therapeutic target and a biomarker for prognosis.

miR-222 targets VGLL4 to promote growth of tongue squamous cell carcinoma

2020 ◽  
Vol 10 (1) ◽  
pp. 102-111
Author(s):  
Liang Shi ◽  
Xiaobin Song ◽  
Ketao Wang ◽  
Shaohua Liu ◽  
Yong Wang
Keyword(s):  
Squamous Cell Carcinoma ◽  
Protein Expression ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Tumor Model ◽  
Tongue Squamous Cell Carcinoma ◽  
Migration And Invasion ◽  
Oral Keratinocytes ◽  
Human Tongue

We investigated whether regulation of VGLL4 by miR-222 affects proliferation, migration, invasion, and apoptosis in human tongue squamous cell carcinoma (TSCC) cells. Nanometer Magnetic beads were prepared to extract RNA in CAL27/human oral keratinocytes (HOK). Correlation between expression of miR-222 and VGLL4 in CAL27/human oral keratinocytes (HOK) was analyzed using RT-PCR and western blot. The cellular effects of miR-222/VGLL4 interactions were detected by cck8, transwell, and cell scratch assays, and flow cytometry after miR-222 was silenced or overexpressed in CAL27 cells. We assessed tumor growth in vivo, in a subcutaneous tumor model in mice, and assessed VGLL4 protein expression in tumors by immunohistochemistry. We found that miR-222 expression is higher in CAL27 cells than that in HOK cells. VGLL4 was highly expressed in HOK cells relative to CAL27 cells. When miR-222 was overexpressed, VGLL4 mRNA expression was reduced in CAL27 cells, and protein expression was reduced in the in vivo tumor model. Thus, miR-222 may down-regulate VGLL4 to promote proliferation, migration, and invasion of TSCC cells.

scholarly journals NF-κB-mediated lncRNA AC007271.3 promotes carcinogenesis of oral squamous cell carcinoma by regulating miR-125b-2-3p/Slug

2020 ◽  
Vol 11 (12) ◽  
Author(s):  
Ze-nan Zheng ◽  
Guang-zhao Huang ◽  
Qing-qing Wu ◽  
Heng-yu Ye ◽  
Wei-sen Zeng ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Molecular Mechanisms ◽  
Nuclear Factor Κb ◽  
Underlying Mechanisms ◽  
E Cadherin

AbstractOral squamous cell carcinoma (OSCC) is the most common oral cancer. The molecular mechanisms of this disease are not fully understood. Our previous studies confirmed that dysregulated function of long non-coding RNA (lncRNA) AC007271.3 was associated with a poor prognosis and overexpression of AC007271.3 promoted cell proliferation, migration, invasion, and inhibited cell apoptosis in vitro, and promoted tumor growth in vivo. However, the underlying mechanisms of AC007271.3 dysregulation remained obscure. In this study, our investigation showed that AC007271.3 functioned as competing endogenous RNA by binding to miR-125b-2-3p and by destabilizing primary miR-125b-2, resulted in the upregulating expression of Slug, which is a direct target of miR-125b-2-3p. Slug also inhibited the expression of E-cadherin but N-cadherin, vimentin, and β-catenin had no obvious change. The expression of AC007271.3 was promoted by the canonical nuclear factor-κB (NF-κB) pathway. Taken together, these results suggested that the classical NF-κB pathway-activated AC007271.3 regulates EMT by miR-125b-2-3p/Slug/E-cadherin axis to promote the development of OSCC, implicating it as a novel potential target for therapeutic intervention in this disease.

scholarly journals LncRNA DANCR promotes the proliferation, migration, and invasion of tongue squamous cell carcinoma cells through miR-135a-5p/KLF8 axis

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Ying Zheng ◽  
Bowen Zheng ◽  
Xue Meng ◽  
Yuwen Yan ◽  
Jia He ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Tumor Growth ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Ectopic Expression ◽  
Underlying Mechanism ◽  
Tongue Squamous Cell Carcinoma ◽  
Migration And Invasion

Abstract Background Tongue squamous cell carcinoma (TSCC) is a most invasive cancer with high mortality and poor prognosis. It is reported that lncRNA DANCR has implications in multiple types of cancers. However, its biological role and underlying mechanism in TSCC progress are not well elucidated. Methods Our present study first investigated the function of DANCR on the proliferation, migration and invasion of TSCC cells by silencing or overexpressing DANCR. Further, the miR-135a-5p-Kruppel-like Factor 8 (KLF8) axis was focused on to explore the regulatory mechanism of DANCR on TSCC cell malignant phenotypes. Xenografted tumor growth using nude mice was performed to examine the role of DANCR in vivo. Results DANCR knockdown reduced the viability and inhibited the migration and invasion of TSCC cells in vitro, while ectopic expression of DANCR induced opposite effects. In vivo, the tumor growth and the expression of matrix metalloproteinase (MMP)-2/9 and KLF8 were also blocked by DANCR inhibition. In addition, we found that miR-135-5p directly targeted DANCR, which was negatively correlated with DANCR on TSCC progression. Its inhibition reversed the beneficial effects of DANCR silence on TSCC malignancies. Furthermore, the expression of KLF8 evidently altered by both DANCR and miR-135a-5p. Silencing KLF8 using its specific siRNA showed that KLF8 was responsible for the induction of miR-135a-5p inhibitor on TSCC cell malignancies and MMP-2/9 expression. Conclusions These findings, for the first time, suggest that DANCR plays an oncogenic role in TSCC progression via targeting miR-135a-5p/KLF8 axis, which provides a promising biomarker and treatment approach for preventing TSCC.

scholarly journals The Chemopreventive Properties and Therapeutic Modulation of Green Tea Polyphenols in Oral Squamous Cell Carcinoma

ISRN Oncology ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Ui-Lyong Lee ◽  
Sung-Weon Choi
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cancer ◽  
Cell Carcinoma ◽  
Green Tea ◽  
Squamous Cell ◽  
Molecular Mechanisms ◽  
Green Tea Polyphenols ◽  
Etiologic Factor

Chemoprevention is a relatively novel and promising approach for controlling cancer that uses specific natural products or synthetic agents to suppress, reverse, or prevent premalignancy before transformation into invasive cancer. Oral cavity squamous cell carcinoma (OCSCC) represents a large, worldwide health burden with approximately 274,000 cases diagnosed annually worldwide. Smoking and alcohol consumption are major inducers of OCSCC. Recently, the human papilloma virus was also shown to potentially be an etiologic factor. Due to its easily identifiable risk factors and the presence of premalignant regions, oral cancer makes a good candidate for chemoprevention. Green tea is the most widely consumed beverage in the world, and it has received considerable attention because of its abundant, scientifically proven, beneficial effects on human health. In this review, we discuss the role of green tea in oral cancer chemoprevention with regard to the multiple molecular mechanisms proposed in various in vitro, in vivo, and clinical trials.

Osimertinib and dihydroartemisinin: A novel drug combination targeting head and neck squamous cell carcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17526-e17526
Author(s):  
Rafael Rosell ◽  
Imane Chaib ◽  
Xueting Cai ◽  
David Llige ◽  
Mariacarmela Santarpia ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Molecular Mechanisms ◽  
Neck Squamous Cell Carcinoma ◽  
Signal Pathways ◽  
Synergistic Cytotoxicity

e17526 Background: Recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) has a dismal prognosis with limited progression-free survival and overall survival, even when treated with different combinations of chemotherapy, targeted therapies and immunotherapy. We explored in vitro and in vivo the effect of the epidermal growth factor (EGFR) inhibitor, osimertinib, alone and in combination with dihydroartemisinin (DHA) in HNSCC. Methods: The combination of osimertinib with DHA was tested in the FaDu and CAL27 HNSCC cell lines. Tumor cell proliferation assays were conducted in cultured cells and mouse xenografts. Western blotting analysis of related signal pathways was performed to investigate the molecular mechanisms of the inhibitory effect of DHA and the combination. Other compounds, which inhibit signal transducer and activator of transcription 3 (STAT3), Src-family kinases (SFKs), sphingosine kinase 1 (SPHK1), or the receptor tyrosine kinase (RTK) AXL were also combined with osimertinib in vitro. Results: Osimertinib exerted synergistic cytotoxicity toward FaDu and CAL27 HNSCC cells when combined with DHA. DHA reversed the osimertinib-induced STAT3 and Src, phosphorylation. The double combination inhibited AXL expression. The anticancer potential of osimertinib plus DHA combination was validated in vivo on FaDu and CAL27 xenografts in mice without notable side effects. Conclusions: The results illustrate that the combinatory therapy of osimertinib and DHA, as a repurposing anticancer drug, could be a novel therapeutic strategy for recurrent and/or metastatic HNSCC patients. The findings indicate that a clinical trial is warranted to confirm the benefit of the combination.

scholarly journals Cathepsin K Is Present in Invasive Oral Tongue Squamous Cell Carcinoma In Vivo and In Vitro

PLoS ONE ◽  
2013 ◽  
Vol 8 (8) ◽  
pp. e70925 ◽  
Author(s):  
Carolina C. Bitu ◽  
Joonas H. Kauppila ◽  
Andréia Bufalino ◽  
Sini Nurmenniemi ◽  
Susanna Teppo ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cathepsin K ◽  
Tongue Squamous Cell Carcinoma ◽  
Oral Tongue

scholarly journals Dihydroartemisinin Inhibits the Proliferation of Esophageal Squamous Cell Carcinoma Partially by Targeting AKT1 and p70S6K

2020 ◽  
Vol 11 ◽  
Author(s):  
Lili Zhu ◽  
Xinhuan Chen ◽  
Yanyan Zhu ◽  
Jiace Qin ◽  
Tingting Niu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Molecular Mechanisms ◽  
Kinase Assay ◽  
Anticancer Effects ◽  
Tumor Tissues

Dihydroartemisinin (DHA), a sesquiterpene lactone with endoperoxide bridge, is one of the derivatives of artemisinin. In addition to having good antimalarial properties, DHA exhibits anticancer effects including against malignant solid tumors. However, the mechanism by which DHA inhibits the progression of esophageal cancer, especially esophageal squamous cell carcinoma (ESCC), is unclear. In this study, DHA was found to inhibit the proliferation of ESCC, and the underlying molecular mechanisms were explored. DHA inhibited ESCC cells proliferation and anchorage-independent growth. Flow cytometry analysis revealed that DHA significantly blocked cell cycle in the G1 phase. The results of human phospho-kinase array revealed that DHA downregulated the levels of p70S6KT389 and p70S6KT421/S424. Furthermore, the levels of mTORS2448, p70S6KT389, p70S6KT421/S424 and RPS6S235/S236 were decreased after DHA treatment in KYSE30 and KYSE150 cells. We then explored the proteins targeted by DHA to inhibit the mTOR-p70S6K-RPS6 pathway. Results of the in vitro kinase assay revealed that DHA significantly inhibited phosphorylation of mTORS2448 by binding to AKT1 and p70S6K kinases. In vivo, DHA inhibited the tumor growth of ESCC patient-derived xenografts and weakened p-mTOR, p-p70S6K, and p-RPS6 expression in tumor tissues. Altogether, our results indicate that DHA has antiproliferative effects in ESCC cells and can downregulate mTOR cascade pathway partially by binding to AKT1 and p70S6K. Thus, DHA has considerable potential for the prevention or treatment of ESCC.

scholarly journals LncRNA MTX2-6 Suppresses Cell Proliferation by Acting as ceRNA of miR-574-5p to Accumulate SMAD4 in Esophageal Squamous Cell Carcinoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Jie Li ◽  
Xu Han ◽  
Yan Gu ◽  
Jixiang Wu ◽  
Jianxiang Song ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Molecular Mechanisms ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Esophageal squamous cell carcinoma (ESCC) has been one of the key causes of cancer deaths worldwide. It has been found that long non-coding RNA (lncRNA) is related to the generation and progression of various cancers (including ESCC). However, there are still many lncRNAs related to ESCC whose functions and molecular mechanisms have not been clearly elucidated. In this study, we first reported that lncRNA MTX2-6 was significantly downregulated in ESCC tissues and cell lines. The decreased expression of MTX2-6 is closely related to larger tumor and worse prognosis of ESCC patients. Through a series of functional experiments, we detected that overexpressed MTX2-6 inhibited cell proliferation and promoted cell apoptosis of ESCC in vitro and in vivo. Further studies showed that MTX2-6 exerts as a competing endogenous RNA (ceRNA) by binding miR-574-5p and elevates the expression of SMAD4 in ESCC. In summary, our results clarify the tumor suppressor roles of MTX2-6/miR-574-5p/SMAD4 axis in the progression of ESCC and provide emerging therapeutic targets for ESCC patients.

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