title: Overexpression of IL-7 enhances cisplatin resistance in glioma.
abstract: Cisplatin is one of the most commonly used chemotherapeutic agents for glioma patients. In this study, array comparative genomic hybridization (aCGH) was used to identify genes associated with cisplatin resistance in a human glioma cell line. The cisplatin-resistant U251/CP2 cell line was derived by stepwise selection using cisplatin. The genetic aberrations of the U251 parental cell line and the U251/CP2 cells were analyzed using aCGH. RT-PCR was used to detect the expression of the altered genes revealed by aCGH. The sensitivity of glioma cells to cisplatin was determined by using the MTT assay. Apoptosis was detected using flow cytometry and western blot analysis. The IC 50 value of cisplatin in U251/CP2 cells was five times higher than its IC 50 in U251 cells. The U251 cells lost at least one copy each of the CFHR1 and CFHR3 genes, and both CFHR1 and CFHR3 were homozygously deleted in U251/CP2 cells. The U251/CP2 cells gained two to three copies of C8orf70 and IL-7 genes. IL-7 mRNA expression was studied in 12 glioma cell lines, and expression was positively correlated with the IC 50 of cisplatin. Furthermore, IL-7 mRNA expression was also positively correlated with the IC 50 of cisplatin in 91 clinical glioma specimens. Additionally, treatment with recombinant human IL-7 (rhIL-7) enhanced cisplatin resistance and increased the relative growth rate of the glioma cells. Moreover, the apoptosis induced by cisplatin could be inhibited by IL-7. In conclusion, our results suggest that IL-7 may play an important role in cisplatin resistance in glioma.
authors.affiliation: State Key Laboratory of Oncology in South China and Department of Neurosurgery/Neuro-oncology, Cancer Center Sun Yat-sen University, Guangzhou, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cui
authors.forename: Jun
authors.initials: J
authors.lastname: Fu
authors.forename: Jesse Chung-Sean
authors.initials: JC
authors.lastname: Pang
authors.forename: Zhi-Kun
authors.initials: ZK
authors.lastname: Qiu
authors.forename: Xiao-Mei
authors.initials: XM
authors.lastname: Liu
authors.forename: Fu-Rong
authors.initials: FR
authors.lastname: Chen
authors.forename: Hong-Liu
authors.initials: HL
authors.lastname: Shi
authors.forename: Ho-Keung
authors.initials: HK
authors.lastname: Ng
authors.forename: Zhong-Ping
authors.initials: ZP
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D055028:Comparative Genomic Hybridization; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D020128:Inhibitory Concentration 50; D015851:Interleukin-7 / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D000970:Antineoplastic Agents; D015851:Interleukin-7; D002945:Cisplatin