Abstract
[Introduction] In order to understand the mechanisms of tumor radioresistance and to develop more effective tumor radiotherapy, we established clinically relevant radioresistant (CRR) cell lines; these continue to proliferate under daily expose to 2 Gy of X-ray. Here, we studied whether CRR cells are cross-resistant to anti-cancer drugs or not using pairs of CRR and their sensitive parental cell lines.
[Method] Compared with parental cell lines, HepG2, HeLa, SAS, KB and H1299 were used, cross resistance of their CRR derivative cell lines, HepG2-R, HeLa-R, SAS-R1, SAS-R2, KB-R and H1299-R were used. Anti-cancer drugs used were cisplatinum (CDDP), docetaxel (DOX), bleomycin, fluorouracil (5-FU), vincristin, etoposide (VP-16) and adriamycin (ADM). Chemosensitivity was analyzed by the high-density survival assay. In addition, RT-PCR was carried out to analyze gene expressions of MDR1.
[Result] 5-FU was effective against all radioresistant cell lines. Six out of 7 (86%) CRR cell lines had cross-resistance to DOC and vincristin. Four (57%) CRR cell lines had cross-resistance to VP-16 and ADM. Overexpression of the MDR1 gene was observed in HepG2-8960-R.
[Discussion] This study suggested that anti-cancer drugs targeting beta-tuburin had little effect for the elimination of clinically relevant radioresistant cells. Not all radioresistant cell lines showed cross-resistance to bleomycin whose action mechanism was similar to X-rays, indicating that contribution of efficient repair of DNA double strand breaks for clinically relevant radioresistance is low.
