Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay.

TLDR

Preclinical anticancer drug discovery has largely relied on testing agents in mice with transplantable leukemias and solid tumors derived from a limited set of murine and human sources. This study investigates the feasibility of a combined in vitro/in vivo screening approach using panels of diverse human tumor cell lines to assess selective cytotoxicity. The microculture tetrazolium assay, applied to 106 diverse human tumor cell lines, showed excellent correlation with protein and viable cell counts (r² 0.89–0.99) and demonstrated reliable growth and drug‑sensitivity measurements over multiple passages, indicating its suitability for early‑stage in vitro drug screening.

Abstract

For the past 30 years strategies for the preclinical discovery and development of potential anticancer agents have been based largely upon the testing of agents in mice bearing transplantable leukemias and solid tumors derived from a limited number of murine as well as human sources. The feasibility of implementing an alternate approach, namely combined in vitro/in vivo screening for selective cytotoxicity among panels of human tumor cell lines derived from a broad spectrum of human solid tumors is under investigation. A group of 30 cell lines acquired from a variety of sources and representing 8 lung cancer pathologies as well as 76 cell lines representing 10 other categories of human cancer (carcinomas of colon, breast, kidney, prostate, ovary, head and neck; glioma; leukemia; melanoma; and sarcoma) have exhibited acceptable growth characteristics and suitable colorimetric profiles in a single, standard culture medium. Measurements of in vitro growth in microculture wells by cell-mediated reduction of tetrazolium showed excellent correlation (0.89 less than r2 less than 0.98) with measurements of cellular protein in adherent cell line cultures as well as viable cell count in suspension cell line cultures (0.94 less than r2 less than 0.99). Since the microculture tetrazolium assay provides sensitive and reproducible indices of growth as well as drug sensitivity in individual cell lines over the course of multiple passages and several months' cultivation, it appears suitable for initial-stage in vitro drug screening.