Cytotoxic effects of the therapeutic radionuclide rhenium-188 combined with taxanes in human prostate carcinoma cell lines

Rogier Lange, Robter T. Heine, Wessel N. Van Wieringen, Adrienne M. Tromp, Mayke Paap, Haiko J. Bloemendal, John M.H. De Klerk, N. Harry Hendrikse, Albert A. Geldof

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Objective: Rhenium-188-HEDP is an effective radiopharmaceutical for the treatment of painful bone metastases from prostate cancer. The effectiveness of the β-radiation emitted by 188Re might be enhanced by combination with chemotherapy, using the radiosensitization concept. Therefore, the authors investigated the combined treatment of the taxanes, docetaxel and cabazitaxel, with 188Re in prostate carcinoma cell lines. Materials and Methods: The cytotoxic effects of single and combined treatment with taxanes and 188Re were investigated in three human prostate carcinoma cell lines (PC-3, DU 145, and LNCaP), using the colony-forming assay. The half maximal effective concentration (EC50) of all individual agents was determined. The combined treatment was studied at 0.25, 0.5, 1, 2, and 4 times the EC50 of each agent. The interaction was investigated with a regression model. Results: The survival curves showed dose-dependent cell growth inhibition for both the taxanes and 188Re. The regression model showed a good capability of explaining the data. It proved additivity in all combination experiments and confirmed a general trend to a slight subadditive effect. Conclusions: This proof-of-mechanism study exploring radiosensitization by combining 188Re and taxanes showed no synergism, but significant additivity. This encourages the design of in vivo studies. Future research should explore the potential added value of concomitant treatment of bone metastases with chemotherapy and 188Re-HEDP.

Original languageEnglish
Pages (from-to)16-23
Number of pages8
JournalCancer Biotherapy and Radiopharmaceuticals
Volume32
Issue number1
DOIs
Publication statusPublished - 1 Feb 2017

Cite this

Lange, Rogier ; Heine, Robter T. ; Van Wieringen, Wessel N. ; Tromp, Adrienne M. ; Paap, Mayke ; Bloemendal, Haiko J. ; De Klerk, John M.H. ; Hendrikse, N. Harry ; Geldof, Albert A. / Cytotoxic effects of the therapeutic radionuclide rhenium-188 combined with taxanes in human prostate carcinoma cell lines. In: Cancer Biotherapy and Radiopharmaceuticals. 2017 ; Vol. 32, No. 1. pp. 16-23.
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abstract = "Objective: Rhenium-188-HEDP is an effective radiopharmaceutical for the treatment of painful bone metastases from prostate cancer. The effectiveness of the β-radiation emitted by 188Re might be enhanced by combination with chemotherapy, using the radiosensitization concept. Therefore, the authors investigated the combined treatment of the taxanes, docetaxel and cabazitaxel, with 188Re in prostate carcinoma cell lines. Materials and Methods: The cytotoxic effects of single and combined treatment with taxanes and 188Re were investigated in three human prostate carcinoma cell lines (PC-3, DU 145, and LNCaP), using the colony-forming assay. The half maximal effective concentration (EC50) of all individual agents was determined. The combined treatment was studied at 0.25, 0.5, 1, 2, and 4 times the EC50 of each agent. The interaction was investigated with a regression model. Results: The survival curves showed dose-dependent cell growth inhibition for both the taxanes and 188Re. The regression model showed a good capability of explaining the data. It proved additivity in all combination experiments and confirmed a general trend to a slight subadditive effect. Conclusions: This proof-of-mechanism study exploring radiosensitization by combining 188Re and taxanes showed no synergism, but significant additivity. This encourages the design of in vivo studies. Future research should explore the potential added value of concomitant treatment of bone metastases with chemotherapy and 188Re-HEDP.",
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author = "Rogier Lange and Heine, {Robter T.} and {Van Wieringen}, {Wessel N.} and Tromp, {Adrienne M.} and Mayke Paap and Bloemendal, {Haiko J.} and {De Klerk}, {John M.H.} and Hendrikse, {N. Harry} and Geldof, {Albert A.}",
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Cytotoxic effects of the therapeutic radionuclide rhenium-188 combined with taxanes in human prostate carcinoma cell lines. / Lange, Rogier; Heine, Robter T.; Van Wieringen, Wessel N.; Tromp, Adrienne M.; Paap, Mayke; Bloemendal, Haiko J.; De Klerk, John M.H.; Hendrikse, N. Harry; Geldof, Albert A.

In: Cancer Biotherapy and Radiopharmaceuticals, Vol. 32, No. 1, 01.02.2017, p. 16-23.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Cytotoxic effects of the therapeutic radionuclide rhenium-188 combined with taxanes in human prostate carcinoma cell lines

AU - Lange, Rogier

AU - Heine, Robter T.

AU - Van Wieringen, Wessel N.

AU - Tromp, Adrienne M.

AU - Paap, Mayke

AU - Bloemendal, Haiko J.

AU - De Klerk, John M.H.

AU - Hendrikse, N. Harry

AU - Geldof, Albert A.

PY - 2017/2/1

Y1 - 2017/2/1

N2 - Objective: Rhenium-188-HEDP is an effective radiopharmaceutical for the treatment of painful bone metastases from prostate cancer. The effectiveness of the β-radiation emitted by 188Re might be enhanced by combination with chemotherapy, using the radiosensitization concept. Therefore, the authors investigated the combined treatment of the taxanes, docetaxel and cabazitaxel, with 188Re in prostate carcinoma cell lines. Materials and Methods: The cytotoxic effects of single and combined treatment with taxanes and 188Re were investigated in three human prostate carcinoma cell lines (PC-3, DU 145, and LNCaP), using the colony-forming assay. The half maximal effective concentration (EC50) of all individual agents was determined. The combined treatment was studied at 0.25, 0.5, 1, 2, and 4 times the EC50 of each agent. The interaction was investigated with a regression model. Results: The survival curves showed dose-dependent cell growth inhibition for both the taxanes and 188Re. The regression model showed a good capability of explaining the data. It proved additivity in all combination experiments and confirmed a general trend to a slight subadditive effect. Conclusions: This proof-of-mechanism study exploring radiosensitization by combining 188Re and taxanes showed no synergism, but significant additivity. This encourages the design of in vivo studies. Future research should explore the potential added value of concomitant treatment of bone metastases with chemotherapy and 188Re-HEDP.

AB - Objective: Rhenium-188-HEDP is an effective radiopharmaceutical for the treatment of painful bone metastases from prostate cancer. The effectiveness of the β-radiation emitted by 188Re might be enhanced by combination with chemotherapy, using the radiosensitization concept. Therefore, the authors investigated the combined treatment of the taxanes, docetaxel and cabazitaxel, with 188Re in prostate carcinoma cell lines. Materials and Methods: The cytotoxic effects of single and combined treatment with taxanes and 188Re were investigated in three human prostate carcinoma cell lines (PC-3, DU 145, and LNCaP), using the colony-forming assay. The half maximal effective concentration (EC50) of all individual agents was determined. The combined treatment was studied at 0.25, 0.5, 1, 2, and 4 times the EC50 of each agent. The interaction was investigated with a regression model. Results: The survival curves showed dose-dependent cell growth inhibition for both the taxanes and 188Re. The regression model showed a good capability of explaining the data. It proved additivity in all combination experiments and confirmed a general trend to a slight subadditive effect. Conclusions: This proof-of-mechanism study exploring radiosensitization by combining 188Re and taxanes showed no synergism, but significant additivity. This encourages the design of in vivo studies. Future research should explore the potential added value of concomitant treatment of bone metastases with chemotherapy and 188Re-HEDP.

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KW - chemotherapy

KW - human cell lines

KW - prostate carcinoma

KW - radiosensitization

KW - rhenium-188

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U2 - 10.1089/cbr.2016.2129

DO - 10.1089/cbr.2016.2129

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JF - Cancer Biotherapy and Radiopharmaceuticals

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