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 IC50 value of cisplatin in U251/CP2 cells was five times higher than its IC50 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 IC50 of cisplatin. Furthermore, IL-7 mRNA expression was also positively correlated with the IC50 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.

Musashi-1 regulates AKT-derived IL-6 autocrinal/paracrinal malignancy and chemoresistance in glioblastoma

“…Several secreted factors, including tumor-associated inflammatory cytokines were shown to regulate autocrine/paracrine signaling in mediating the malignant transformation of tumor cells including chemoresistance [26–28]. To explore the potential targets involving in MSI1-driven tumor-resistance in malignant glioma, we sought to in silico analyze the global gene expression profile to explore the impact of MSI1 overexpression in GBM cells.…”

Interleukin 6 augments lung cancer chemotherapeutic resistance via ataxia‐telangiectasia mutated/NF‐kappaB pathway activation

“…Chemotherapeutic agents can not only induce tumor cell apoptosis but also trigger inflammation in the tumor microenvironment . Proinflammatory factors, such as IL‐2, IL‐7 and IL‐6, are documented to be involved in MDR in head and neck squamous cells, glioma cells, prostate cancer, lung cancer and breast cancer . Meanwhile, a higher level of circulating IL‐6, increased by chemotherapeutic agent treatment, is associated with patients' survival in gastric carcinoma, prostate cancer, breast cancer and lung cancer, indicating that MDR is influenced by the level of IL‐6 .…”

“…(26) Proinflammatory factors, such as IL-2, IL-7 and IL-6, are documented to be involved in MDR in head and neck squamous cells, glioma cells, prostate cancer, lung cancer and breast cancer. (10,(27)(28)(29)(30) Meanwhile, a higher level of circulating IL-6, increased by chemotherapeutic agent treatment, is associated with patients' survival in gastric carcinoma, prostate cancer, breast cancer and lung cancer, (7,8,(31)(32)(33) indicating that MDR is influenced by the level of IL-6. (25,27,34) Hence, despite the higher level of vascular endothelial growth factor contributing to the upregulation of anti-apoptotic protein and ABCG2 (Fig.…”

IL‐7–Mediated IL‐7R‐JAK3/STAT5 signalling pathway contributes to chemotherapeutic sensitivity in non–small‐cell lung cancer

“…However, IL‐7 was found to have no effect on tumour growth in mice colon carcinoma and cell resistance to oxaliplatin in CT26 cells . In glioma cells, IL‐7 has a pro‐tumour role with the enhanced cisplatin resistance and decreased cell apoptosis induced by cisplatin . The pro‐tumour roles of IL‐7 were also reported in NSCLC for promoting the metastatic process .…”