Effect of combining anti-epidermal growth factor receptor antibody C225 and radiation on DU145 prostate cancer

Wagener, Matthew; Zhang, Xiaochun; Villarreal, Humberto; Levy, L.B.; Allen, Pamela K.; Shentu, Shujun; Fang, Bingliang; Krishnan, Sunil; Chang, Joe Y.; Cheung, Min Rex

doi:10.3892/or.19.5.1071

Cited by 4 publications

(5 citation statements)

References 34 publications

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“…However, the suppression of colony formation in A431 cells was significantly increased by cetuximab alone treatment (SF 0.81, p < 0.001). Wagener et al showed that cetuximab increases the susceptibility of DU145 cells to radiation treatment, but the additional effect was not significant [17]. These results could not be fully verified in the colony formation assay carried out in this study.…”

Section: Discussioncontrasting

confidence: 67%

“…Therefore, an additional antiproliferative effect was only expected in the DU145 prostate carcinoma cell line by cetuximab [16]. In a report by Wagener et al and Liu et al a moderate suppressive effect on proliferation rate by either radiation or cetuximab alone has been observed in DU 145 prostate carcinoma cells which was more pronounced in combination [17,18].…”

Section: Introductionmentioning

confidence: 95%

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Functional and mutational analysis after radiation and cetuximab treatment on prostate carcinoma cell line DU145

et al. 2021

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Background Epidermal Growth Factor Receptor is often overexpressed in advanced prostate carcinoma. In-vitro-studies in prostate carcinoma cell line DU145 have demonstrated increased sensibility to radiation after cetuximab treatment, but clinical data are not sufficient to date. Methods We analyzed effects of radiation and cetuximab in DU145 and A431 using proliferation, colony-forming-unit- and annexin-V-apoptosis-assays. Changes in protein expression of pEGFR and pERK1/2 after radiation and cetuximab treatment were analyzed. Using NGS we also investigated the impact of cetuximab long-term treatment. Results Cell counts in DU145 were reduced by 44% after 4 Gy (p = 0.006) and 55% after 4 Gy and cetuximab (p < 0.001). The surviving fraction (SF) was 0.69 after 2 Gy, 0.41 after 4 Gy and 0.15 after 6 Gy (each p < 0.001). Cetuximab treatment did not alter significantly growth reduction in 4 Gy radiated DU145 cells, p > 0.05 or SF, p > 0.05, but minor effects on apoptotic cell fraction in DU145 were detected. Using western blot, there were no detectable pEGFR and pERK1/2 protein signals after cetuximab treatment. No RAS mutation or HER2 amplification was detected, however a TP53 gen-mutation c.820G > T was found. Conclusions Radiation inhibits cell-proliferation and colony-growth and induces apoptosis in DU145. Despite blocking MAP-Kinase-pathway using cetuximab, no significant radiation-sensitizing-effect was detected. Cetuximab treatment did not induce resistance-mutations. Further research must clarify which combination of anti-EGFR treatment strategies can increase radiation-sensitizing-effects.

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Section: Discussioncontrasting

confidence: 67%

Section: Introductionmentioning

confidence: 95%

Functional and mutational analysis after radiation and cetuximab treatment on prostate carcinoma cell line DU145

et al. 2021

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“…The DU145 cell line is known to express EGFR and secrete EGF which acts via an autocrine method to stimulate growth (22). Inhibition of EGFR has been shown to enhance radiation response in a variety of cell lines including the DU145 cell line (23). It is possible that inhibition of this autocrine signaling pathway with AZD6244 treatment contributed to the observed increase in radiation sensitivity.…”

Section: Discussionmentioning

confidence: 99%

In vitro and In vivo Radiosensitization with AZD6244 (ARRY-142886), an Inhibitor of Mitogen-activated Protein Kinase/Extracellular Signal-regulated Kinase 1/2 Kinase

Chung

Brown

Asano

et al. 2009

Clinical Cancer Research

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Purpose: The mitogen-activated protein (MAP) kinase pathway is important for cell proliferation, survival, and differentiation, and is frequently up-regulated in cancers. The MAP kinase pathway is also activated after exposure to ionizing radiation. We investigated the effects of AZD6244 (ARRY-142886), an inhibitor of MAP kinase/extracellular signal-regulated kinase 1/2, on radiation response. Experimental Design: The effects of AZD6244 on the in vitro radiosensitivity of human cancer cell lines (A549, MiaPaCa2, and DU145) were evaluated using clonogenic assays. DNA damage repair was evaluated using gH2AX, and mitotic catastrophe was measured using nuclear fragmentation. Cell cycle effects were measured with flow cytometry. Growth delay was used to evaluate the effects of AZD6244 on in vivo tumor radiosensitivity. Results: Exposure of each cell line to AZD6244 before irradiation resulted in an increase in radiosensitivity with dose enhancement factors at a surviving fraction of 0.1, ranging from 1.16 to 2.0. No effects of AZD6244 on radiation-induced apoptosis or persistence of gH2AX foci after irradiation were detected. Cells treated with AZD6244 had an increased mitotic index and decreased Chk1phosphorylation at 1and 2 hours after irradiation. Mitotic catastrophe was increased in cells receiving AZD6244 and irradiation compared with the single treatments. In vivo studies revealed that AZD6244 administration to mice bearing A549 tumor xenografts resulted in a greater than additive increase in radiation-induced tumor growth delay (dose enhancement factor of 3.38). Conclusions: These results indicate that AZD6244 can enhance tumor cell radiosensitivity in vitro and in vivo and suggest that this effect involves an increase in mitotic catastrophe.

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“…Studies had shown that in addition to mitochondrial mediated reduction, other factors such as serum and membrane enzymes may also affect the bioreduction of tetrazolium compounds (Geys et al, 2010; Knight and Dancis, 2006; Kuhn et al, 2003). These factors may be responsible for the higher error reported by other laboratories (Wagener et al, 2008). …”

Section: Introductionmentioning

confidence: 90%

Hydroxyethyl disulfide as an efficient metabolic assay for cell viability in vitro

Zhang

Ward

et al. 2012

Toxicology in Vitro

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Cell viability assays have a variety of well known practical and technical limitations. All the available approaches have disadvantages, such as non-linearity, high background and cumbersome protocols. Several commonly used tetrazolium chemicals rely upon generation of a colored formazan product formed by mitochondrial reduction of these compounds via phenazine methosulfate (PMS). However, sensitivity is inherently limited because their reduction relies on mitochondrial bioreduction and cellular transport of PMS, as well as accessibility to tetrazolium chemicals. In this study, we identify hydroxethyldisulfide (HEDS) as an inexpensive probe that can measure cellular metabolic activity without the need of PMS. In tissue culture medium, HEDS accurately quantitated metabolically active live cells in a linear manner superior to tetrazolium based and other assays. Cell toxicity produced by chemotherapeutics (cisplatin, etoposide), oxidants (hydrogen peroxide, acetaminophen), toxins (Phenyl arsine oxide, arsenite) or ionizing radiation was rapidly determined by the HEDS assay. We found that HEDS was superior to other commonly used assays for cell viability determinations in its solubility, membrane permeability, and intracellular conversion to a metabolic reporter that is readily transported into the extracellular medium. Our findings establish the use of HEDS in a simple, rapid and low cost assay to accurately quantify viable cells.

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Effect of combining anti-epidermal growth factor receptor antibody C225 and radiation on DU145 prostate cancer

Cited by 4 publications

References 34 publications

Functional and mutational analysis after radiation and cetuximab treatment on prostate carcinoma cell line DU145

Functional and mutational analysis after radiation and cetuximab treatment on prostate carcinoma cell line DU145

In vitro and In vivo Radiosensitization with AZD6244 (ARRY-142886), an Inhibitor of Mitogen-activated Protein Kinase/Extracellular Signal-regulated Kinase 1/2 Kinase

Hydroxyethyl disulfide as an efficient metabolic assay for cell viability in vitro

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