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Chemosensitivity Testing of Human Colorectal Carcinoma Cell Lines Using a Tetrazolium-based Colorimetric Assay¹

National Cancer Institute-Navy Medical Oncology Branch, Naval Hospital, Bethesda, Maryland 20814-5105 [J-G. P., B. S. K., J. C., J. D. M., A. F. G.], and Biostatistics and Data Management Section, Clinical Oncology Program [S. M. S.] and Clinical Pharmacology Branch [J. M. C.], National Cancer Institute, Bethesda, Maryland 20892

The in vitro chemosensitivity of 11 human colorectal cell lines to seven chemotherapeutic 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.

¹ The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Navy or the Department of Defense.

² To whom requests for reprints should be addressed, at Department of Surgery, College of Medicine, Seoul National University and Seoul National University Hospital, Seoul, 110, Korea.

³ Present address: Department of Clinical Oncology, Newcastle General Hospital, Newcastle, England.

Received 2/ 2/87. Revised 5/20/87. Accepted 8/ 3/87.

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