Chemosensitivity testing of human colorectal carcinoma cell lines using a tetrazolium-based colorimetric assay

J. G. Park, B. S. Kramer, S. M. Steinberg, J. Carmichael, J. M. Collins, J. D. Minna, A. F. Gazdar

Research output: Contribution to journalArticle

181 Citations (Scopus)

Abstract

The in vitro chemosensitivity of 11 human colorectal cell lines to seven chemotherapeutics agents was determined using a semiautomated tetrazolium-based colorimetric assay (MTT assay). Four of the cell lines were from primary tumors and seven from metastases. Eight lines were from patients with no prior chemotherapy. From assay results, we predict 5-fluorouracil (5-FU) to be the sole active agent of the seven tested. This is based on two observations: the range of drug concentrations which produced 50% inhibition of cell growth was greatest with 5-FU (388-fold versus 5- to 30-fold with the other six agents); and the area under the curve (AUC) which produced 50% growth inhibition was within a clinically achievable range only for 5-FU. Since the assay AUC of 5-FU at 50% inhibition was in a clinically achievable range for only two of the 11 cell lines, we performed a multivariate analysis to explore parameters which predict 5-FU sensitivity. In the best fitting model, sensitivity was positively correlated with cloning efficiency in media and with cell surface TAG-72 (a tumor-associated glycoprotein found on epithelial tumors of ovary, lung, colon, and breast origin) expression. If validated with an in vivo test such as the nude mouse model, the MTT assay could be very useful in new drug screening for colorectal carcinoma, for examining combination chemotherapy for synergy, for exploring strategies for biochemical modulation, and perhaps in individualizing therapy when cell lines can be established from a patient.

Original languageEnglish (US)
Pages (from-to)5875-5879
Number of pages5
JournalCancer Research
Volume47
Issue number22
StatePublished - 1987

Fingerprint

Fluorouracil
Colorectal Neoplasms
Cell Line
Area Under Curve
Neoplasms
Preclinical Drug Evaluations
Growth
Combination Drug Therapy
Nude Mice
Organism Cloning
Ovary
Glycoproteins
Colon
Breast
Multivariate Analysis
Neoplasm Metastasis
Drug Therapy
Lung
Pharmaceutical Preparations
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Park, J. G., Kramer, B. S., Steinberg, S. M., Carmichael, J., Collins, J. M., Minna, J. D., & Gazdar, A. F. (1987). Chemosensitivity testing of human colorectal carcinoma cell lines using a tetrazolium-based colorimetric assay. Cancer Research, 47(22), 5875-5879.

Chemosensitivity testing of human colorectal carcinoma cell lines using a tetrazolium-based colorimetric assay. / Park, J. G.; Kramer, B. S.; Steinberg, S. M.; Carmichael, J.; Collins, J. M.; Minna, J. D.; Gazdar, A. F.

In: Cancer Research, Vol. 47, No. 22, 1987, p. 5875-5879.

Research output: Contribution to journalArticle

Park, JG, Kramer, BS, Steinberg, SM, Carmichael, J, Collins, JM, Minna, JD & Gazdar, AF 1987, 'Chemosensitivity testing of human colorectal carcinoma cell lines using a tetrazolium-based colorimetric assay', Cancer Research, vol. 47, no. 22, pp. 5875-5879.
Park, J. G. ; Kramer, B. S. ; Steinberg, S. M. ; Carmichael, J. ; Collins, J. M. ; Minna, J. D. ; Gazdar, A. F. / Chemosensitivity testing of human colorectal carcinoma cell lines using a tetrazolium-based colorimetric assay. In: Cancer Research. 1987 ; Vol. 47, No. 22. pp. 5875-5879.
@article{e4bb1637e74c40cb8d6a63eaeb3f0955,
title = "Chemosensitivity testing of human colorectal carcinoma cell lines using a tetrazolium-based colorimetric assay",
abstract = "The in vitro chemosensitivity of 11 human colorectal cell lines to seven chemotherapeutics agents was determined using a semiautomated tetrazolium-based colorimetric assay (MTT assay). Four of the cell lines were from primary tumors and seven from metastases. Eight lines were from patients with no prior chemotherapy. From assay results, we predict 5-fluorouracil (5-FU) to be the sole active agent of the seven tested. This is based on two observations: the range of drug concentrations which produced 50{\%} inhibition of cell growth was greatest with 5-FU (388-fold versus 5- to 30-fold with the other six agents); and the area under the curve (AUC) which produced 50{\%} growth inhibition was within a clinically achievable range only for 5-FU. Since the assay AUC of 5-FU at 50{\%} inhibition was in a clinically achievable range for only two of the 11 cell lines, we performed a multivariate analysis to explore parameters which predict 5-FU sensitivity. In the best fitting model, sensitivity was positively correlated with cloning efficiency in media and with cell surface TAG-72 (a tumor-associated glycoprotein found on epithelial tumors of ovary, lung, colon, and breast origin) expression. If validated with an in vivo test such as the nude mouse model, the MTT assay could be very useful in new drug screening for colorectal carcinoma, for examining combination chemotherapy for synergy, for exploring strategies for biochemical modulation, and perhaps in individualizing therapy when cell lines can be established from a patient.",
author = "Park, {J. G.} and Kramer, {B. S.} and Steinberg, {S. M.} and J. Carmichael and Collins, {J. M.} and Minna, {J. D.} and Gazdar, {A. F.}",
year = "1987",
language = "English (US)",
volume = "47",
pages = "5875--5879",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "22",

}

TY - JOUR

T1 - Chemosensitivity testing of human colorectal carcinoma cell lines using a tetrazolium-based colorimetric assay

AU - Park, J. G.

AU - Kramer, B. S.

AU - Steinberg, S. M.

AU - Carmichael, J.

AU - Collins, J. M.

AU - Minna, J. D.

AU - Gazdar, A. F.

PY - 1987

Y1 - 1987

N2 - The in vitro chemosensitivity of 11 human colorectal cell lines to seven chemotherapeutics agents was determined using a semiautomated tetrazolium-based colorimetric assay (MTT assay). Four of the cell lines were from primary tumors and seven from metastases. Eight lines were from patients with no prior chemotherapy. From assay results, we predict 5-fluorouracil (5-FU) to be the sole active agent of the seven tested. This is based on two observations: the range of drug concentrations which produced 50% inhibition of cell growth was greatest with 5-FU (388-fold versus 5- to 30-fold with the other six agents); and the area under the curve (AUC) which produced 50% growth inhibition was within a clinically achievable range only for 5-FU. Since the assay AUC of 5-FU at 50% inhibition was in a clinically achievable range for only two of the 11 cell lines, we performed a multivariate analysis to explore parameters which predict 5-FU sensitivity. In the best fitting model, sensitivity was positively correlated with cloning efficiency in media and with cell surface TAG-72 (a tumor-associated glycoprotein found on epithelial tumors of ovary, lung, colon, and breast origin) expression. If validated with an in vivo test such as the nude mouse model, the MTT assay could be very useful in new drug screening for colorectal carcinoma, for examining combination chemotherapy for synergy, for exploring strategies for biochemical modulation, and perhaps in individualizing therapy when cell lines can be established from a patient.

AB - The in vitro chemosensitivity of 11 human colorectal cell lines to seven chemotherapeutics agents was determined using a semiautomated tetrazolium-based colorimetric assay (MTT assay). Four of the cell lines were from primary tumors and seven from metastases. Eight lines were from patients with no prior chemotherapy. From assay results, we predict 5-fluorouracil (5-FU) to be the sole active agent of the seven tested. This is based on two observations: the range of drug concentrations which produced 50% inhibition of cell growth was greatest with 5-FU (388-fold versus 5- to 30-fold with the other six agents); and the area under the curve (AUC) which produced 50% growth inhibition was within a clinically achievable range only for 5-FU. Since the assay AUC of 5-FU at 50% inhibition was in a clinically achievable range for only two of the 11 cell lines, we performed a multivariate analysis to explore parameters which predict 5-FU sensitivity. In the best fitting model, sensitivity was positively correlated with cloning efficiency in media and with cell surface TAG-72 (a tumor-associated glycoprotein found on epithelial tumors of ovary, lung, colon, and breast origin) expression. If validated with an in vivo test such as the nude mouse model, the MTT assay could be very useful in new drug screening for colorectal carcinoma, for examining combination chemotherapy for synergy, for exploring strategies for biochemical modulation, and perhaps in individualizing therapy when cell lines can be established from a patient.

UR - http://www.scopus.com/inward/record.url?scp=0023554218&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023554218&partnerID=8YFLogxK

M3 - Article

VL - 47

SP - 5875

EP - 5879

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 22

ER -