Targeting COX-2 potently inhibits proliferation of cancer cells in vivo but not in vitro in cutaneous squamous cell carcinoma

Background: Cutaneous squamous cell carcinoma (cSCC) incidence continues to rise with increasing morbidity and mortality, with limited treatment options for advanced disease. Future improvements in targeted therapy will rely on advances in genomic/transcriptomic understanding and the use of model systems for basic research. We describe here the panel of 16 primary and metastatic cSCC cell lines developed and characterised over the past three decades in our laboratory in order to provide such a resource for future preclinical research and drug screening. Methods: Primary keratinocytes were isolated from cSCC tumours and metastases, and cell lines were established. These were characterised using short tandem repeat (STR) profiling and genotyped by whole exome sequencing. Multiple in vitro assays were performed to document their morphology, growth characteristics, migration and invasion characteristics, and in vivo xenograft growth. Results: STR profiles of the cSCC lines allow the confirmation of their unique identity. Phylogenetic trees derived from exome sequence analysis of the matched primary and metastatic lines provide insight into the genetic basis of disease progression. The results of in vivo and in vitro analyses allow researchers to select suitable cell lines for specific experimentation. Conclusions: There are few well-characterised cSCC lines available for widespread preclinical experimentation and drug screening. The described cSCC cell line panel provides a critical tool for in vitro and in vivo experimentation.

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Combination of the natural compound Periplocin and TRAIL induce esophageal squamous cell carcinoma apoptosis in vitro and in vivo: Implication in anticancer therapy

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-019-1498-z ◽

2019 ◽

Vol 38 (1) ◽

Cited By ~ 2

Author(s):

Lujuan Han ◽

Suli Dai ◽

Zhirong Li ◽

Cong Zhang ◽

Sisi Wei ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Esophageal Cancer ◽

Esophageal Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Cancer Cells ◽

Squamous Cell ◽

Natural Compound ◽

Synergistic Activity

Abstract Background Esophageal cancer is one of the most common malignant tumors in the world. With currently available therapies, only 20% ~ 30% patients can survive this disease for more than 5 years. TRAIL, a natural ligand for death receptors that can induce the apoptosis of cancer cells, has been explored as a therapeutic agent for cancers, but it has been reported that many cancer cells are resistant to TRAIL, limiting the potential clinical use of TRAIL as a cancer therapy. Meanwhile, Periplocin (CPP), a natural compound from dry root of Periploca sepium Bge, has been studied for its anti-cancer activity in a variety of cancers. It is not clear whether CPP and TRAIL can have activity on esophageal squamous cell carcinoma (ESCC) cells, or whether the combination of these two agents can have synergistic activity. Methods We used MTS assay, flow cytometry and TUNEL assay to detect the effects of CPP alone or in combination with TRAIL on ESCC cells. The mechanism of CPP enhances the activity of TRAIL was analyzed by western blot, dual luciferase reporter gene assay and chromatin immunoprecipitation (ChIP) assay. The anti-tumor effects and the potential toxic side effects of CPP alone or in combination with TRAIL were also evaluated in vivo. Results In our studies, we found that CPP alone or in combination with TRAIL could inhibit the proliferation of ESCC cells and induce apoptosis, and we certificated that combination of two agents exert synergized functions. For the first time, we identified FoxP3 as a key transcriptional repressor for both DR4 and DR5. By down-regulating FoxP3, CPP increases the expression of DR4/DR5 and renders ESCC cells much more sensitive to TRAIL. We also showed that CPP reduced the expression of Survivin by inhibiting the activity of Wnt/β-catenin pathway. All these contributed to synergistic activity of CPP and TRAIL on ESCC cells in vitro and in vivo. Conclusion Our data suggest that CPP and TRAIL could be further explored as potential therapeutic approach for esophageal cancer.

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Clinicopathological roles of S100A8 and S100A9 in cutaneous squamous cell carcinoma in vivo and in vitro

Archives of Dermatological Research ◽

10.1007/s00403-014-1453-y ◽

2014 ◽

Vol 306 (5) ◽

pp. 489-496 ◽

Cited By ~ 15

Author(s):

Dae-Kyoung Choi ◽

Zheng Jun Li ◽

In-Kyu Chang ◽

Min-Kyung Yeo ◽

Jin-Man Kim ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Cutaneous Squamous Cell Carcinoma

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Plasma Treatment Limits Cutaneous Squamous Cell Carcinoma Development In Vitro and In Vivo

Cancers ◽

10.3390/cancers12071993 ◽

2020 ◽

Vol 12 (7) ◽

pp. 1993 ◽

Cited By ~ 2

Author(s):

Gabriella Pasqual-Melo ◽

Thiago Nascimento ◽

Larissa Juliani Sanches ◽

Fernanda Paschoal Blegniski ◽

Julya Karen Bianchi ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Plasma Treatment ◽

Cell Carcinoma ◽

Squamous Cell ◽

Healthcare Services ◽

Skin Lesions ◽

Cutaneous Squamous Cell Carcinoma ◽

High Rate

Cutaneous squamous cell carcinoma (SCC) is the most prevalent cancer worldwide, increasing the cost of healthcare services and with a high rate of morbidity. Its etiology is linked to chronic ultraviolet (UV) exposure that leads to malignant transformation of keratinocytes. Invasive growth and metastasis are severe consequences of this process. Therapy-resistant and highly aggressive SCC is frequently fatal, exemplifying the need for novel treatment strategies. Cold physical plasma is a partially ionized gas, expelling therapeutic doses of reactive oxygen and nitrogen species that were investigated for their anticancer capacity against SCC in vitro and SCC-like lesions in vivo. Using the kINPen argon plasma jet, a selective growth-reducing action of plasma treatment was identified in two SCC cell lines in 2D and 3D cultures. In vivo, plasma treatment limited the progression of UVB-induced SSC-like skin lesions and dermal degeneration without compromising lesional or non-lesional skin. In lesional tissue, this was associated with a decrease in cell proliferation and the antioxidant transcription factor Nrf2 following plasma treatment, while catalase expression was increased. Analysis of skin adjacent to the lesions and determination of global antioxidant parameters confirmed the local but not systemic action of the plasma anticancer therapy in vivo.

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Abstract 4686:MALis down-regulated in oral squamous cell carcinoma and suppresses proliferation, invasion, tumorigenicity of oral cancer cells,in vitro and in vivo

10.1158/1538-7445.am10-4686 ◽

2010 ◽

Author(s):

Wantao Chen ◽

Wei Cao ◽

Ping Zhang

Keyword(s):

Squamous Cell Carcinoma ◽

Oral Cancer ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Cancer Cells ◽

Squamous Cell ◽

Oral Cancer Cells

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The effectiveness and safety of X-PDT for cutaneous squamous cell carcinoma and melanoma

Nanomedicine ◽

10.2217/nnm-2019-0094 ◽

2019 ◽

Vol 14 (15) ◽

pp. 2027-2043 ◽

Cited By ~ 10

Author(s):

Lei Shi ◽

Pei Liu ◽

Jing Wu ◽

Lun Ma ◽

Han Zheng ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Acute Toxicity ◽

Cell Carcinoma ◽

Squamous Cell ◽

Microvessel Density ◽

Cutaneous Squamous Cell Carcinoma ◽

X Ray ◽

B16f10 Cells

Aim: To clarify the effectiveness and safety of x-ray-activated photodynamic therapy (X-PDT) for cutaneous squamous cell carcinoma (SCC) and melanoma. Materials & methods: Copper-cysteamine nanoparticles were used as a photosensitizer of X-PDT. The dark toxicity and cytotoxicity were studied in vitro. Tumor volume, microvessel density and acute toxicity of mice were evaluated in vivo. Results: Without x-ray irradiation, copper-cysteamine nanoparticles were nontoxic for keratinocyte cells. XL50 cells (SCC) were more sensitive to X-PDT than B16F10 cells (melanoma). X-PDT successfully inhibited the growth of SCC in vivo (p < 0.05), while the B16F10 melanoma was resistant. Microvessel density in SCC tissue was remarkably reduced (p < 0.05). No obvious acute toxicity reaction was observed. Conclusion: X-PDT is a safe and effective treatment for SCC.

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Comparison of in vivo and in vitro prostaglandin E production by squamous cell carcinoma of the head and neck

Otolaryngology ◽

10.1016/s0194-5998(94)70590-9 ◽

1994 ◽

Vol 111 (3) ◽

pp. 189-196 ◽

Cited By ~ 10

Author(s):

C SNYDERMAN ◽

I KLAPAN ◽

M MILANOVICH ◽

D HEO ◽

R WAGNER ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Prostaglandin E

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Cyclosporine A Suppresses the Malignant Progression of Oral Squamous Cell Carcinoma in vitro

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520618666181029170605 ◽

2019 ◽

Vol 19 (2) ◽

pp. 248-255 ◽

Cited By ~ 2

Author(s):

Ling Gao ◽

Jianwei Dong ◽

Nanyang Zhang ◽

Zhanxian Le ◽

Wenhao Ren ◽

...

Keyword(s):

Cell Cycle ◽

Squamous Cell Carcinoma ◽

Oral Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Cyclosporine A ◽

Migration And Invasion ◽

Signal Molecules ◽

Cox 2

Background:The Oral Squamous Cell Carcinoma (OSCC) is one of the most frequent cancer types. Failure of treatment of OSCC is potentially lethal because of local recurrence, regional lymph node metastasis, and distant metastasis. Chemotherapy plays a vital role through suppression of tumorigenesis. Cyclosporine A (CsA), an immunosuppressant drug, has been efficiently used in allograft organ transplant recipients to prevent rejection, and also has been used in a subset of patients with autoimmunity related disorders. The present study aims to investigate novel and effective chemotherapeutic drugs to overcome drug-resistance in the treatment of OSCC.Methods:Cells were incubated in the standard way. Cell viability was assayed using the MTT assay. Cell proliferation was determined using colony formation assay. The cell cycle assay was performed using flow cytometry. Apoptosis was assessed using fluorescence-activated cell sorting after stained by the Annexin V-fluorescein isothiocyanate (FITC). Cell migration and invasion were analyzed using wound healing assay and tranwell. The effect of COX-2, c-Myc, MMP-9, MMP-2, and NFATc1 protein expression was determined using Western blot analysis while NFATc1 mRNA expression was determined by RT-PCR.Results:In vitro studies indicated that CsA inhibited partial OSCC growth by inducing cell cycle arrest, apoptosis, and the migration and invasion of OSCC cells. We also demonstrated that CsA could inhibit the expression of NFATc1 and its downstream genes COX-2, c-Myc, MMP-9, and MMP-2 in OSCC cells. Furthermore, we analyzed the expression of NFATc1 in head and neck cancer through the Oncomine database. The data was consistent with the experimental findings.Conclusion:The present study initially demonstrated that CsA could inhibit the progression of OSCC cells and can mediate the signal molecules of NFATc1 signaling pathway, which has strong relationship with cancer development. That explains us CsA has potential to explore the possibilities as a novel chemotherapeutic drug for the treatment of OSCC.

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Pan-ERBB kinase inhibition augments CDK4/6 inhibitor efficacy in oesophageal squamous cell carcinoma

Gut ◽

10.1136/gutjnl-2020-323276 ◽

2021 ◽

pp. gutjnl-2020-323276

Author(s):

Jin Zhou ◽

Zhong Wu ◽

Zhouwei Zhang ◽

Louisa Goss ◽

James McFarland ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Large Scale ◽

Cell Cancer ◽

Oesophageal Squamous Cell Carcinoma ◽

Squamous Cancer ◽

Striking Success

ObjectiveOesophageal squamous cell carcinoma (OSCC), like other squamous carcinomas, harbour highly recurrent cell cycle pathway alterations, especially hyperactivation of the CCND1/CDK4/6 axis, raising the potential for use of existing CDK4/6 inhibitors in these cancers. Although CDK4/6 inhibition has shown striking success when combined with endocrine therapy in oestrogen receptor positive breast cancer, CDK4/6 inhibitor palbociclib monotherapy has not revealed evidence of efficacy to date in OSCC clinical studies. Herein, we sought to elucidate the identification of key dependencies in OSCC as a foundation for the selection of targets whose blockade could be combined with CDK4/6 inhibition.DesignWe combined large-scale genomic dependency and pharmaceutical screening datasets with preclinical cell line models, to identified potential combination therapies in squamous cell cancer.ResultsWe identified sensitivity to inhibitors to the ERBB family of receptor kinases, results clearly extending beyond the previously described minority of tumours with EGFR amplification/dependence, specifically finding a subset of OSCCs with dual dependence on ERBB3 and ERBB2. Subsequently. we demonstrated marked efficacy of combined pan-ERBB and CDK4/6 inhibition in vitro and in vivo. Furthermore, we demonstrated that squamous lineage transcription factor KLF5 facilitated activation of ERBBs in OSCC.ConclusionThese results provide clear rationale for development of combined ERBB and CDK4/6 inhibition in these cancers and raises the potential for KLF5 expression as a candidate biomarker to guide the use of these agents. These data suggested that by combining existing Food and Drug Administration (FDA)-approved agents, we have the capacity to improve therapy for OSCC and other squamous cancer.

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JOSD1 promotes proliferation and chemoresistance of head and neck squamous cell carcinoma under the epigenetic regulation of BRD4

Cancer Cell International ◽

10.1186/s12935-021-02060-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Chao Jing ◽

Dandan Liu ◽

Qingchuan Lai ◽

Linqi Li ◽

Mengqian Zhou ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Gene Expression Omnibus ◽

Neck Squamous Cell Carcinoma ◽

The Cancer Genome Atlas ◽

In Vivo Experiments

Abstract Background Deubiquitinating enzymes (DUBs) play critical roles in various cancers by modulating functional proteins post-translationally. Previous studies have demonstrated that DUB Josephin Domain Containing 1 (JOSD1) is implicated in tumor progression, however, the role and mechanism of JOSD1 in head and neck squamous cell carcinoma (HNSCC) remain to be explored. In this study, we aimed to identify the clinical significance and function of JOSD1 in HNSCC. Methods The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were analyzed to find novel DUBs in HNSCC. Immunohistochemistry assay was performed to determine the expression of JOSD1 in our cohort of 42 patients suffered with HNSCC. Kaplan–Meier analysis was used to identify the correlation between JOSD1 and the prognosis of HNSCC patients. The regulation of BRD4 on JOSD1 was determined by using pharmacological inhibition and gene depletion. The in vitro and in vivo experiments were conducted to elucidate the role of JOSD1 in HNSCC. Results The results of IHC showed that JOSD1 was aberrantly expressed in HNSCC specimens, especially in the chemoresistant ones. The overexpression of JOSD1 indicated poor clinical outcome of HNSCC patients. Moreover, JOSD1 depletion dramatically impaired cell proliferation and colony formation, and promoted cisplatin-induced apoptosis of HNSCC cells in vitro. Additionally, JOSD1 suppression inhibited the tumor growth and improved chemosensitivity in vivo. The epigenetic regulator BRD4 contributed to the upregulation of JOSD1 in HNSCC. Conclusions These results demonstrate that JOSD1 functions as an oncogene in HNSCC progression, and provide a promising target for clinical diagnosis and therapy of HNSCC.

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