L1EPO, a novel podophyllotoxin derivative overcomes P-glycoprotein-mediated multidrug resistance in K562/A02 cell line.
The ineffectiveness of anticancer drugs is frequently observed in cancer chemotherapy. The resistance of tumor cells to various cytotoxic drugs is defined as multidrug resistance (MDR). The purpose of our present study was to investigate the inhibitory effects of L1EPO synthesized by our group on P-glycoprotein (P-gp)-mediated MDR in K562/A02 and KBv200 cell lines, which expressed high levels of P-gp. Both the cytotoxicity of the compound and its ability to inhibit K562/A02 and KBv200 cells were determined by sulforhodamine B sodium salt (SRB) assay. Morphologic apoptosis was detected by Hoechst33342 staining assay. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect mdr-1 gene transcription, and Western blot assay was used to assess P-gp expression. Interestingly, we found that the K562/A02 cell line was rendered resistant toward Adriamycin but not towards L1EPO when compared with the parental cells. Furthermore, L1EPO could down-regulate the mdr-1 gene, and it reduced the expression of P-gp and displayed a perfect dose dependence. Moreover, it had less cytotoxicity in normal human cell lines (fibroblast, VEC), GI(50)>10 micromol/l. Consequently, L1EPO has the potential to overcome P-glycoprotein-mediated MDR in the K562/A02 cell line.
Chen
Hong
H
Medical College of Chinese People's Armed Police Forces, China.
Wang
Jing
J
Zhang
Jingze
J
Wang
Yizheng
Y
Cao
Bo
B
Bai
Shufang
S
Yu
Peng-Fei
PF
Bi
Wenchao
W
Xie
Wenli
W