Effects of paclitaxel in combination with radiation on human head and neck cancer cells (ZMK-1), cervical squamous cell carcinoma (CaSki), and breast adenocarcinoma cells (MCF-7)

Abstract Background The cytotoxic effect of radiation plays an important role in the treatment of head and neck cancer. However, irradiation is known to lead to the migration of various cancer cells, including those of head and neck cancer. Recently, fibroblasts in the cancer microenvironment have been reported to be involved in this mechanism. Nevertheless, the mechanism underlying the migration of head and neck cancer cells remains unclear. The purpose of this study was to elucidate this migration mechanism induced by irradiation in terms of the interaction of head and neck cancer cells with fibroblasts. Methods We used the head and neck squamous cell carcinoma (HNSCC) cell lines SAS and FaDu as well as fibroblast cell lines. These cells were irradiated and their viability was compared. In fibroblasts, changes in interleukin-6 (IL-6) secretion caused by irradiation were measured by enzyme-linked immunosorbent assay (ELISA). The cell migration ability of cancer cells was evaluated via a migration assay using a semipermeable membrane. HNSCC cells were cocultured with irradiated and nonirradiated fibroblasts, and their migration ability under each condition was compared. We also examined the effect of IL-6 on the migration of HNSCC cells. Furthermore, to investigate the effect of fibroblast-derived IL-6 on the migration ability of HNSCC cells, we conducted a coculture study using IL-6 neutralizing antibody. Results Irradiation reduced the survival of HNSCC cells, whereas fibroblasts were resistant to irradiation. Irradiation also increased IL-6 secretion by fibroblasts. Migration of HNSCC cells was enhanced by coculture with fibroblasts and further enhanced by coculture with irradiated fibroblasts. We also confirmed that the migration of HNSCC cells was induced by IL-6. The enhanced migration of cancer cells caused by coculturing with fibroblasts was canceled by the IL-6 neutralizing antibody. Conclusion These results show that fibroblasts survive irradiation and induce the migration ability of HNSCC cells through increased secretion of IL-6.

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Radiosensitivity of Head and Neck Cancer Cells In Vitro: A 96-Well Plate Clonogenic Cell Assay for Squamous Cell Carcinoma

Archives of Otolaryngology - Head and Neck Surgery ◽

10.1001/archotol.1988.01860160071024 ◽

1988 ◽

Vol 114 (4) ◽

pp. 427-431 ◽

Cited By ~ 24

Author(s):

R. Grenman ◽

D. Burk ◽

E. Virolainen ◽

J. G. Wagner ◽

A. S. Lichter ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Head And Neck Cancer ◽

Cell Carcinoma ◽

Head And Neck ◽

Cancer Cells ◽

Neck Cancer ◽

Squamous Cell ◽

Cell Assay ◽

Clonogenic Cell

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Specific Targeting of HER2-Positive Head and Neck Squamous Cell Carcinoma Line HN5 by Idarubicin-ZHER2 Affibody Conjugate

Current Cancer Drug Targets ◽

10.2174/1568009617666170427105417 ◽

2018 ◽

Vol 19 (1) ◽

pp. 65-73 ◽

Cited By ~ 5

Author(s):

Marzieh Ghanemi ◽

Aminollah Pourshohod ◽

Mohammad Ali Ghaffari ◽

Alireza kheirollah ◽

Mansour Amin ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Cell Line ◽

Squamous Cell ◽

Optimum Concentration ◽

Her2 Positive ◽

Affibody Molecules ◽

Specific Targeting ◽

Mcf 7

Background:Expression of human epidermal growth factor receptor type 2 (HER2) in head and neck squamous cell carcinoma (HNSCC) cell line HN5 can be employed with great opportunities of success for specific targeting of anti-cancer chemotherapeutic agents.Objective:In the current study, HER2-specific affibody molecule, ZHER2:342 (an engineered protein with great affinity for HER2 receptors) was selected for conjugation to idarubicin (an anti-neoplastic antibiotic).Method:ZHER2:342 affibody gene with one added cysteine code at the its 5′ end was synthesized de novo and then inserted into pET302 plasmid and transferred to E. Coli BL21 hosting system. After induction of protein expression, the recombinant ZHER2 affibody molecules were purified using Ni- NTA resin and purity was analyzed through SDS-PAGE. Affinity-purified affibody molecules were conjugated to idarubicin through a heterobifunctional crosslinker, sulfosuccinimidyl 4-(Nmaleimidomethyl) cyclohexane-1-carboxylate (Sulfo-SMCC). Specific toxicity of idarubicin-ZHER2 affibody conjugate against two HER2-positive cells, HN5 and MCF-7 was assessed through MTT assay after an exposure time of 48 hours with different concentrations of conjugate.Results:Idarubicin in the non-conjugated form showed potent toxic effects against both cell lines, while HN5 cells were significantly more sensitive compared to MCF-7 cells. Dimeric ZHER2 affibody showed a mild decreasing effect on growth of both HN5 and MCF-7 cells at optimum concentration. Idarubicin-ZHER2 affibody conjugate at an optimum concentration reduced viability of HN5 cell line more efficiently compared to MCF-7 cell line.In conclusion, idarubicin-ZHER2 affibody conjugate in optimum concentrations can be used for specific targeting and killing of HN5 cells.

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