Further characterization of two distinct adriamycin-resistant sublines from LoVo human colon carcinoma cells.
We previously reported that two multidrug resistant sublines, AdR1.2 and SRA1.2, derived from LoVo human colon carcinoma cells, apparently expressed different resistance phenotypes including differential expression of p-glycoprotein (Pgp). Here, we further examined and compared other potential resistance mechanisms between AdR1.2 and SRA1.2 resistant cells. Our results showed that the Pgp-mediated AdR1.2 cells possessed an activated drug efflux pump and decreased nucleus binding of Adriamycin, while the non-Pgp-mediated SRA1.2 cells only held the second feature. Verapamil, however, partially reversed resistance in both sublines. Although glutathione-s-transferase was overexpressed in AdR1.2 but not in SRA1.2, both sublines had lower susceptibilities to drug-induced DNA strand breaks and greater capacities to repair such damage than did LoVo cells. These data suggest that, despite the differences in multidrug resistance phenotypes, the features of decreased susceptibility to DNA damage and enhanced DNA repair capacities may represent the common mechanisms responsible for drug resistance in both Pgp- and non-Pgp-mediated multidrug resistant cells.
Yang
L Y
LY
Division of Laboratory Medicine, University of Texas, M.D. Anderson Cancer Center, Houston 77030.
Trujillo
J M
JM
Su
Y Z
YZ
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002467:Cell Nucleus / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D004249:DNA Damage; D004260:DNA Repair; D004317:Doxorubicin / Q000493:pharmacokinetics* / Q000494:pharmacology; D004351:Drug Resistance; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D004317:Doxorubicin; D014700:Verapamil; D005982:Glutathione Transferase