RT Journal Article
SR Electronic
T1 Induction of Cross-resistance to ABCB1 Substrates in Venetoclax-resistant Human Leukemia HL60 Cells
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 4239
OP 4248
DO 10.21873/anticanres.15228
VO 41
IS 9
A1 YUKO NAKAYAMA
A1 KOHJI TAKARA
A1 TETSUYA MINEGAKI
A1 KAZUHIRO YAMAMOTO
A1 TOMOHIRO OMURA
A1 IKUKO YANO
YR 2021
UL http://ar.iiarjournals.org/content/41/9/4239.abstract
AB Background/Aim: Resistance to venetoclax, a selective inhibitor of BCL2 apoptosis regulator (BCL2), is regarded as a clinical problem. However, it is unclear whether resistance to venetoclax induces cross-resistance to other drugs. Materials and Methods: Venetoclax-resistant HL60/VEN cells were newly established through continuous exposure of human acute promyelocytic leukemia HL60 cells to venetoclax, and drug sensitivity, apoptotic activity, and mRNA expression were compared between HL60 and HL60/VEN cells. Results: HL60/VEN cells displayed approximately 3-fold resistance to venetoclax, maintained their ability to synthesize DNA and had low apoptotic activity. HL60/VEN cells also exhibited diverse sensitivity to cytotoxic drugs, especially resistance to ATP binding cassette subfamily B member 1 (ABCB1) substrates, and up-regulation of ABCB1 mRNA. However, the sensitivity of HL60/VEN cells to venetoclax was not restored by ABCB1 inhibitor. ABCB1-overexpressing cells did not show resistance to venetoclax. Conclusion: HL60/VEN cells exhibited up-regulation of ABCB1 in addition to an alteration in apoptotic activity, and cross-resistance to ABCB1 substrates was clarified. However, sensitivity to venetoclax was hardly affected by ABCB1.