Inhibition of telomerase activity as a measure of tumor cell killing by cisplatin in squamous cell carcinoma cell line

Background: Telomerase is a ribonucleoprotein enzyme which is involved in t he maintenance of chromosome ends. Telomerase activity is frequently associ ated with malignant phenotypes, and it can be considered a ubiquitous tumor marker. In this study we describe an approach for developing in vitro chem osensitivity assays based on the assessment of telomerase activity in squam ous cell carcinoma to treatment with anticancer drugs. Methods: We used A43 1/CDDP1 and A431/CDDP2, two previously established cisplatin (CDDP)-resista nt A431 sublines. These cell lines were not multidrug resistant but specifi cally resistant to the CDDP drug family. The telomeric repeat amplification protocol (TRAP assay) was used to measure telomerase activity in CDDP-resi stant cell lines and to examine the effect of CDDP and other anticancer dru gs on enzyme levels. We next analyzed the relations between telomerase acti vity and cytotoxic effects of CDDP in human squamous cell carcinoma (HSC2, HSC3, HSC4 and KB cell lines). Results: The telomerase activity of A431/CDD P1 and A431/ CDDP2 was significantly higher than that of the parent A431 ce ll (A431/P) treated with CDDP and carboplatin at IC50. On the other hand, t elomerase activity in these cell lines was not influenced by treatment with 5-fluorouracil, bleomycin, Adriamycin or taxol. The regression line derive d from the quantitative analysis of the telomeric ladder versus IC50 of CDD P concentrations was analyzed. Telomerase activity was found to be positive ly correlated with the IC50 values for CDDP. Conclusions: The results of th e present studies on in vitro squamous cell carcinoma cell lines indicate t hat telomerase activity inhibition can be used as a marker of tumor cell ki lling by CDDP. Therefore, the present investigation provides a rational bas is for an in vitro chemosensitivity assay based on telomerase activity eval uation. Copyright (C) 2001 S. Karger AG, Basel.