Decreased sensitivity of multidrug-resistant tumor cells to cisplatin is correlated with sorcin gene co-amplification.
A set of multidrug resistant (MDR) murine leukemia P388 sublines processing 30-50-fold mdr1 gene amplification was obtained as a result of experimental chemotherapy with rubomycin, ruboxyl, vinblastine, vincristine, or combination of rubomycin and vincristine. Significant differences of developed MDR sublines in response to treatment with cisplatin, tiophosphamide, sarcolysin, and dopad were found. Strong correlation between drug sensitivity and a copy number of gene coding for 19-22 kDa calcium-binding sorcin gene co-amplification were hypersensitive to cisplatin and alkylating agents, the cell sublines showing amplification of sorcin DNA sequences did not possess such collateral sensitivity and even acquired cross-resistance. The dependence of sensitivity to cisplatin on sorcin gene co-amplification was confirmed by analysis of Djungarian hamster DM15 cell sublines that selected for MDR in vitro by colchicine.
Demidova
N S
NS
Institute of Chemical Physics at Chernogolovka, Russian Academy of Sciences.
Ilyinskaya
G V
GV
Shiryaeva
O A
OA
Chernova
O B
OB
Goncharova
S A
SA
Kopnin
B P
BP
D000477:Alkylating Agents / Q000494:pharmacology*; D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics*; D002461:Cell Line, Transformed; D002945:Cisplatin / Q000494:pharmacology*; D006224:Cricetinae; D018432:Drug Resistance, Multiple / Q000235:genetics*; D005347:Fibroblasts; D005784:Gene Amplification / Q000235:genetics*; D007941:Leukemia P388 / Q000188:drug therapy / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*
D000477:Alkylating Agents; D002135:Calcium-Binding Proteins; D009363:Neoplasm Proteins; D002945:Cisplatin