Similar chromosomal changes in cisplatin and oxaliplatin-resistant sublines of the H69 SCLC cell line are not associated with platinum resistance.
Small cell lung cancer (SCLC) initially responds well to DNA damaging drugs such as cisplatin, however this is transitory as resistance normally develops. To investigate whether changes in chromosomal copy number caused by platinum drug treatment contributes to platinum resistance, we have analyzed H69 SCLC cells and two low-level platinum-resistant sublines, H69CIS200 and H69OX400, derived by cisplatin and oxaliplatin treatment, respectively. Affymetrix 10K SNP array showed that cisplatin and oxaliplatin have independently caused similar changes including loss of segments 6q21-qter and 13pter-13q.14.11 and duplication of chromosome 21. Interestingly, despite using equally cytotoxic doses of drug in the development of the cell lines, oxaliplatin caused three times more chromosomal changes than cisplatin. The resistant cell lines lose their resistant phenotype after 3 months of drug-free culture. The revertant cell lines, denoted H69CIS200-S and H69OX400-S, were also analyzed by Affymetrix array to determine if chromosomal changes associated with resistance remain after the resistant phenotype is lost. In the H69OX400-S many of the changes observed in the resistant cells were absent suggesting that they contributed to the resistant phenotype including: loss of 1q23.3-qter, 10q11.23, and 19q13.12-q13.2 and duplication of segments 6p21.2-p12.3, 16q12.1-16q13, 16q21-q23.1, and 19q12. However, out of the similar changes induced by cisplatin and oxaliplatin, both the loss of 6q21-qter and gain of 21 were still present in the H69CIS200-S and H69OX400-S cells. This suggests that cisplatin and oxaliplatin induced similar changes due to inherent vulnerabilities in the H69 cells rather than changes associated with platinum resistance.
Stordal
Britta
B
Bill Walsh Cancer Research Laboratories, Royal North Shore Hospital, St Leonards, Sydney, NSW 2065, Australia.
Peters
Greg
G
Davey
Ross
R
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018288:Carcinoma, Small Cell / Q000235:genetics*; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations / Q000187:drug effects; D002945:Cisplatin / Q000627:therapeutic use*; D020732:Cytogenetic Analysis; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D018628:Gene Dosage; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D009944:Organoplatinum Compounds / Q000627:therapeutic use*; D000077150:Oxaliplatin; D020641:Polymorphism, Single Nucleotide
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D002945:Cisplatin