Correlation of chemosensitivity to anticancer drugs and telomere length, telomerase activity and telomerase RNA expression in human ovarian cancer cells.

BACKGROUND

We examined the correlations among telomere length (TRF), telomerase activity (TA) and the steady-state level of telomerase RNA expression (hTR) of human ovarian cancer cells with different phenotypes and investigated whether the cells' sensitivities to anticancer agents correlate with TRF, TA or hTR.

MATERIALS AND METHODS

The TRF, TA and hTR of 11 human ovarian cancer cell lines and 2 cisplatin-resistant ovarian cancer cell lines were determined by genomic Southern blotting, a telomeric repeat amplification protocol and reverse transcription-polymerase chain reaction. The chemosensitivities of the cell lines to cisplatin (CDDP), paclitaxel (TAX), etoposide (ETO), CPT-11 (CPT), cyclophosphamide (CYC), ifomide (IFO) and doxorubicin (DOX) were decided as IC50 values by calorimetric assay.

RESULTS

All 11 cell lines presented shorter mean TRFs (5.0 kb) than normal control tissue (8.0 kb); 10 cell lines presented a 3.2-fold higher mean TA than the control and all 11 cell lines expressed hTR. Quantitatively, the steady-state levels of hTR correlated with the TRF (p < 0.05). Significant positive correlations between hTR and CDDP sensitivities (at 24 hours of exposure), ETO (72 hours), CPT (48 hours) and CYC/IFO (24-72 hours) were observed. The same was true for TRF and the CDDP sensitivities (at 24 hours). TAX and DOX did not have any impact on these factors. The TRF, TA and hTR values in the two CDDP-resistant cell lines were generally reduced, compared to their parent cell lines.

CONCLUSIONS

Alkylating agents (CDDP, CYC and IFO) and topoisomerase inhibitors (ETO, CPT) may have the potential to influence the structural alteration of hTRs and telomeres and thus, the down-regulation of the TA in ovarian cancer cells.