【Objective】To investigate whether excision repair cross-complementing rodent repair deficiency gene 2 (ERCC2）expression correlates with drug resistance in human tumor cell lines utilized by the anticancer drug screening program of the National Cancer Institute (NCI).【Methods】With Western blot analysis,ERCC2 protein levels of 60 human tumor cell lines were determined and compared with the patterns of cytotoxicity (determined by sulforhodamine-B assay) of 170 anticancer drugs.【Results】ERCC2 protein levels had a wide range of expression including undetectable levels in 6 cell lines.ERCC2 protein levels were found to be significantly correlated with resistance of the tumor cells to 28 out of 170 chemotherapeutic agents.Considering the mechanism of action,ERCC2 expression was significantlyrelated toresistance of thetumor cells toalkylatingagents or tubulin-active antimitotic agents.【Conclusion】The present study suggests that ERCC2,and perhaps NER in general,is a contributing factor to alkylating agents and tubulin-active antimitotic agents resistance in human tumor cell lines.

Background and Objective: The histone deacetylase inhibitor,trichostatin A(TSA),was shown to induce apoptosis in transformed cells at submicromolar concentrations. However, the effect of TSA on brain tumor cells is still unknown. This study was designed to investigate whether TSA posses antitumor activity and if any, its mechanism. Materials and Methods: A p53 mutant human glioma cell line T98G and a p53 wild type human neuroblastoma cell line SKNSH were exposed to TSA. Cell proliferation was assessed by sulforhodamine B (SRB) cytotoxicity assay. Apoptosis was quantified by flow cytometry and confirmed by apoptotic ladder formation. Expression patterns of accumulation of highly acetylated histone H3,H4; p53 and cell cycle-associated p21waf,p27 which were induced by TSA were determined by using Western blot analysis. Results: TSA inhibited the proliferation of brain tumor cell lines at nanomolar concentrations and induced accumulation of highly acetylased histone moleculars. Treatment with TSA at 0.33μ M for 24h significantly induced cell apoptosis.In addition to the suppression of cell growth, the up regulation of p21waf and p27 expression was observed within 48h after the treatment.p21 protein levels were increased at early time points and reached maximal levels at 8h, while p27 protein levels were increased after 8h. However, there was no significant changes of acetylased p53 and endogenous p53 protein levels were observed. Conclusion:TSA may inhibit brain tumor cell growth in vitro, which is otherwise particularly resistant to chemotherapy. TSA acts as an anti-tumor agent could be through co-operation between p21 and p27 in growth inhibition, irrespective of endogenous p53 status.