AIM:To Investigate the specific mechanisms of intrinsic andacquired resistance to taxotere(TXT)in pancreaticadenocarcinoma(PAC).METHODS:MIT assay was used to detect the sensitivity ofPAC cell line SUIT-2 and its sublines(S-007,S-013,S-020,S-028 and TXT selected SUIT-2 cell line,S2/TXT)to TXT.Mdr1(P-gp),multidrug resistance associated protein(MRP),lung resistance protein(LRP)and β-tubulin isotypegene expressions were detected by RT-PCR.Thefunctionality of P-gp and MRP was tested using their specificblocker vorapamil(Ver)and indomethacin(IMC),respectively.The transporter activity of P-gp was alsoconfirmed by Rhodamine 123 accumulation assay.RESULTS:S-020 and S2/TXT were found to be significantlyresistant to TXT(19 and 9.5-fold to their parental cell lineSUIT-2,respectively).RT-PCR demonstrated strongexpression of Mdr1 in these two cell lines,but weakerexpression or no expression in other cells lines.MRP andLRP expressions were found In most of these cell lines.TheTXT-resistance in S2-020 and S2/TXT could be reversedalmost completely by Ver,but not by IMC.Flow cytometryshowed that Ver increased the accumulation of Rhodamine-123 in these two cell lines.Compared with S-020 and SUIT-2,the levels of β-tubulin isotype Ⅱ,Ⅲ expressions in S-2/TXTwere Increased remarkably.CONCLUSION:The both intrinsic and acquired TXT-relateddrug resistance in these PAC cell lines is mainly mediated byP-gp,but had no relationship to MRP and LRP expressions.The increases of β-tubulin isotypa Ⅱ,Ⅲ might be collateralchanges that occur when the SUIT-2 cells are treated withTXT.
