Reversal effect of BM-cyclin 1 on multidrug resistance in C-A120 cells.
In this study, multidrug-resistant human epidermoid C-A120 cells and the sensitive parental KB cells were used as experimental models. BM-cyclin 1, a traditional antimycoplasma drug, was tested to explore the reversal effect of multidrug resistance and its mechanisms in these cell lines. The MTT analysis showed that BM-cyclin 1 could reverse multidrug resistance effectively in C-A120 cells; the sensitivity of C-A120 cells to adriamycin, etoposide and cisplatin was enhanced by 6.0, 8.2 and 1.7 times, respectively. Immunoblotting analysis and reverse transcription-polymerase chain reaction were used to study the BM-cyclin 1-induced changes in topoisomerase IIalpha. The results showed that the expression of topoisomerase IIalpha in treated C-A120 cells increased significantly. Topoisomerase II catalytic activity increased by 30% compared with the untreated cells, as measured by decatenation of kinetopolast DNA. Immunoblotting analysis also indicated the transcription factor levels of specificity: those of protein 1 (Sp1) and nuclear factor-YA increased after treatment with BM-cyclin 1, whereas the mRNA and protein expression of multidrug resistance protein 2 was significantly downregulated. These results demonstrated that BM-cyclin 1 could effectively reverse the multidrug resistance of C-A120 cells by increasing the expression of topoisomerase IIalpha and by suppressing the expression of multidrug resistance protein 2, strongly suggesting that BM-cyclin 1 is a potential multidrug resistance reversal agent.
Wang
Lin
L
State Key Laboratory of Oncology in Southern China.
Sun
Jian
J
Li
Yong-Qiang
YQ
Chen
Zhe-Sheng
ZS
Akiyama
Shin-Ichi
S
Xian
Li-Jian
LJ
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004250:DNA Topoisomerases, Type II / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D004224:Diterpenes / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D015151:Immunoblotting; D008911:Minocycline / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000097202:ATP-Binding Cassette Sub-Family B Member 4
D018435:ATP Binding Cassette Transporter, Subfamily B; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D004224:Diterpenes; D008911:Minocycline; D000097202:ATP-Binding Cassette Sub-Family B Member 4; C074450:BM-cyclin