FaDu cell characteristics induced by multidrug resistance

Ma, Jincai; Lu, Sumei; Lan, Yu; Tian, Jiajun; Li, Jianfeng; Wang, Haibo; Xu, Wei

doi:10.3892/or.2011.1418

Cited by 4 publications

(6 citation statements)

References 17 publications

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“…FaDu/T was developed and determined as previously described (17). FaDu and FaDu/T cells were cultured as a monolayer on Dulbecco’s Modified Eagle’s Medium (DMEM; Gibco) containing 10% fetal calf serum, 100 U/ml penicillin and 100 mg streptomycin at 37°C in a humidified atmosphere composed of 95% air and 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

“…Acridine orange (AO) staining and Hoechst/PI double staining were conducted as previously described (17). …”

Section: Methodsmentioning

confidence: 99%

“…Protein extraction and western blotting were conducted as previously described (17). Bands for β-actin, Twist1, cleaved caspase-3, cleaved caspase-9, Bcl-2 and Bax were visualized at apparent molecular weights of 43, 170, 28, 17, 37, 26 and 23 kDa, respectively.…”

Section: Methodsmentioning

confidence: 99%

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Role and mechanism of Twist1 in modulating the chemosensitivity of FaDu cells

et al. 2014

Molecular Medicine Reports

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Multidrug resistance (MDR) is one of the most important obstacles affecting the efficacy of chemotherapy treatments for numerous types of cancer. In the present study, we have demonstrated the possible function of Twist1 in the chemosensitivity of head and neck squamous cell carcinoma (HNSCC) and have identified that its mechanism maybe associated with MDR1/P-gp regulation. To investigate this, the hypopharyngeal cancer cell line, FaDu, and its MDR cell line induced by taxol, FaDu/T, were employed. Stable transfectants targeted to Twist1 overexpression and Twist1 silencing based on FaDu were also conducted. Morphological observation, flow cytometry, reverse transcription-polymerase chain reaction (RT-PCR), western blotting and laser scanning confocal microscope detection were utilized to detect the associations between Twist1 and the chemosensitivity of FaDu cells. Our results demonstrated that Twist1 and MDR1/P-gp were upregulated in FaDu/T cells in a MDR dose-dependent manner. The anti-apoptotic capabilities of FaDu/T cells were enhanced during MDR progression, with apoptosis-related proteins (Bcl-2, Bax, activated caspase-3 and caspase-9) changing to resist apoptosis. Twist1 overexpression decreased the sensitivity of cells to taxol as revealed by a significant increase in MDR1/P-gp and IC50 (P<0.05). This overexpression also enhanced the resistance to apoptosis, with apoptotic proteins changing to resist cell death, and inhibited Ca2+ release induced by taxol (P<0.05). Detections in Twist1 silencing cells also confirmed this result. This study provided evidence that alterations of Twist1 expression modulates the chemosensitivity of FaDu cells to taxol. Therefore, Twist1 knockdown may be a promising treatment regimen for advanced hypopharyngeal carcinoma patients with MDR.

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Section: Methodsmentioning

confidence: 99%

“…Acridine orange (AO) staining and Hoechst/PI double staining were conducted as previously described (17). …”

Section: Methodsmentioning

confidence: 99%

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Role and mechanism of Twist1 in modulating the chemosensitivity of FaDu cells

et al. 2014

Molecular Medicine Reports

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“…The predominant therapy for hypopharyngeal carcinoma remains confined to surgery with additional treatments of radiotherapy and chemotherapy (1). Although surgical techniques and anticancer agents have advanced, the overall survival rates have not significantly improved during the last two decades (2,3). Therefore, identification of the associated target factors and the potential mechanism of hypopharyngeal carcinoma metastasis and proliferation are important for the survival of patients.…”

Section: Introductionmentioning

confidence: 99%

Epithelial cell adhesion molecule is overexpressed in hypopharyngeal carcinoma and suppresses the metastasis and proliferation of the disease when downregulated

et al. 2014

Oncology Letters

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The epithelial cell adhesion molecule (EpCAM) is overexpressed in the majority of human epithelial carcinomas, and its overexpression is associated with proliferation and neoplastic transformation. However, the precise molecular mechanism involved in EpCAM-related proliferation and metastasis in hypopharyngeal carcinoma is unknown. The aim of the present study was to identify the role of EpCAM in the metastasis and proliferation of hypopharyngeal carcinoma. An immunohistochemical staining assay indicated that EpCAM was overexpressed in primary hypopharyngeal carcinoma tissues, and that this overexpression correlated with the tumor size and lymph node metastasis. In the following treatment of the hypopharyngeal carcinoma FaDu cell line with EpCAM, the downregulation of EpCAM was found to significantly suppress cell metastasis and proliferation, as detected by Transwell, clone formation and MTT assays. Additionally, western blot analysis revealed that EpCAM downregulation increased the expression of the adhesion- and proliferation-related factors, E-cadherin, α-catenin and β-catenin, in the cytoskeleton, as well as β-catenin expression in the nucleus. In conclusion, the present study indicated that EpCAM is a potential oncogene and contributes to the metastasis of hypopharyngeal carcinoma. The current study is the first to provide evidence for the potential value of targeting EpCAM in hypopharyngeal carcinoma therapy.

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“…In head and neck cancers (HNCs) that affect the pharynx—an organ essential to the ability to swallow and to speak—surgery is often problematic, particularity in the late stages of the cancer [3,4]. Due to the significant patient morbidity associated with surgical treatment and an increasing trend towards organ preservation strategies, treatments with an emphasis on organ preservation and restoration have become more common [5,6]. Thus, chemotherapy is preferential.…”

Section: Introductionmentioning

confidence: 99%

The Limitations of Collagen/CPP Hybrid Peptides as Carriers for Cancer Drugs to FaDu Cells

Morfin

Slowinska

2019

Molecules

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The in vitro efficacy of cancer prodrugs varies significantly between malignant cell lines. The most commonly identified problems relate to delivery: uptake mechanism, endosomal entrapment, and drug release. Here we present the study of collagen/cell penetrating hybrid (COL/CPP) peptide carriers intended to deliver paclitaxel to the hypopharyngeal carcinoma (FaDu) cells. Confocal microscopy imaging revealed the surprising response of FaDu cell to COL/CPP in comparison to previously studied cancer cell lines: hybrid peptides that carry both COL and CPP domain adsorb on the FaDu cell surface. While the CPP domain was design to facilitate the cellular uptake, in the case of FaDu cells, it also induced detrimental interactions with the cell membrane. Despite surface adsorption, the colocalization study with endosomal markers EEA1 and LAMP1 reveals that COL/CPP is internalized via endosomal pathway, peptides are able to escape before lysosome formation and release paclitaxel. Therefore, the main obstacle for paclitaxel delivery to FaDu cells appears to be related to cell surface properties. This behavior seems specific to FaDu cells, and could be linked to previously reported overexpression of T5, heparanase splice variants that produces protein lacking enzymatic activity of heparanase. This results in increased concentration of HSPG on FaDu cell surface, and possibly creates a barrier for cellular uptake of highly charged COL/CPP.

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FaDu cell characteristics induced by multidrug resistance

Cited by 4 publications

References 17 publications

Role and mechanism of Twist1 in modulating the chemosensitivity of FaDu cells

Role and mechanism of Twist1 in modulating the chemosensitivity of FaDu cells

Epithelial cell adhesion molecule is overexpressed in hypopharyngeal carcinoma and suppresses the metastasis and proliferation of the disease when downregulated

The Limitations of Collagen/CPP Hybrid Peptides as Carriers for Cancer Drugs to FaDu Cells

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