In Vitro Sensitivity and Resistance of Cultured Human Squamous Carcinoma Cells to Cis-Platinum and Methotrexate

Abstract

To determine whether resistance to chemotherapy in advanced head and neck squamous cell carcinoma stems from biochemical mechanisms and to assess the potential usefulness of new anticarcinogens, an in vitro test would be highly desirable. In the past 4 years our laboratory has developed methodology to establish squamous carcinoma cell lines in tissue culture from patients with squamous cancer of the head and neck. We used some of these lines to compare the in vitro effects of methotrexate on squamous carcinoma, fibrosarcoma, and melanoma cells. Three of the squamous carcinoma lines were tested for sensitivity to both methotrexate and cis-platinum; all but one squamous carcinoma cell line exposed to methotrexate showed growth inhibition at the physiologically attainable concentration of 10−7 M. In contrast, a tenfold higher concentration was required to produce similar effects in the melanoma, while no concentration inhibited fibrosarcoma growth. Cis-platinum showed consistent squamous carcinoma cytotoxicity in 10–5 M and 10–6 M concentrations. This approach should be useful for determining the relative sensitivity and resistance of head and neck cancers to chemotherapeutic agents in vitro.