[Chemosensitivity of mdr1 gene overexpressed multidrug resistant cancer cells to lidamycin].
OBJECTIVE
To investigate the chemosensitivity to lidamycin (C-1027) in mdr1 gene overexpressing cancer cell lines established by drug induction and by gene-transfection.


METHODS
DNA was cloned by RT-PCR and then eukaryotic expressing recombinant plasmid pcDNA3. 1/mdrl was constructed. Using Lipofectamine 2000, a strain of stably transfected human hepatoma cancer cells, HepG2/mdrl, was obtained. The mdr1 mRNA level, P-glycoprotein (P-gp) level and the activity of P-gp to extrude drugs in cancer cells were determined by RT-PCR, immunofluorescence analysis and rhodamine 123 efflux assay. The chemosensitivity of cancer cells with low or high mdr1 expression to lidamycin and other antitumor drugs was tested by MTT assay.


RESULTS
The mdr1 mRNA and P-gp levels in KBv200, MCF-7/ADR, and stably transfected HepG2/mdr1 cells were much higher than that in respective parent KB, MCF-7 and HepG2 cells. The IC50 values of lidamycin for KBv200, MCF-7/ADR and HepG2/mdrl cells were (0.24 +/- 0.20) nmol x L(-1), (0.028 +/- 0.011) nmol x L(-1), and (0.020 +/- 0.011) nmol x L(-1), respectively. Compared with parental cells, the values of resistant fold for KBv200, MCF-7/ADR and HepG2/mdr1 cells to lidamycin were 6.8, 1.6 and 1.3 fold; to adriamycin were 37.2, 181.3 and 8.8 fold; to taxol were 336.8, 49.2 and 40.3 fold, respectively.


CONCLUSIONS
Lidamycin is highly active to multidrug resistant cancer cells. The chemosensitivity of those resistant cancer cells to lidamycin is approximately at the similar level as that of parent cancer cells.
Shi
Yi-Kang
YK
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Wu
Shu-Ying
SY
Huang
Yun-Hong
YH
Zhen
Yong-Su
YS
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis / Q000235:genetics*; D000617:Aminoglycosides / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D053281:Enediynes / Q000494:pharmacology*; D019450:Genes, MDR; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014162:Transfection
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000617:Aminoglycosides; D000903:Antibiotics, Antineoplastic; D053281:Enediynes; C058024:C 1027