Advanced Search
YANG Dongyi, BU Xingyao, YAN Zhaoyue, QU Mingqi, MA Chunxiao, ZHANG Hui. GM-CSF Enhances Effect of TMZ on High-grade Glioma Cells[J]. Cancer Research on Prevention and Treatment, 2016, 43(2): 100-105. DOI: 10.3971/j.issn.1000-8578.2016.02.002
Citation: YANG Dongyi, BU Xingyao, YAN Zhaoyue, QU Mingqi, MA Chunxiao, ZHANG Hui. GM-CSF Enhances Effect of TMZ on High-grade Glioma Cells[J]. Cancer Research on Prevention and Treatment, 2016, 43(2): 100-105. DOI: 10.3971/j.issn.1000-8578.2016.02.002

GM-CSF Enhances Effect of TMZ on High-grade Glioma Cells

More Information
  • Received Date: February 24, 2015
  • Revised Date: July 08, 2015
  • Objective To investigate the effect of granulocyte-macrophage colony-stimulating factor (GMCSF) combined with temozolomide (TMZ) on high-grade glioma cells and related mechanism. Methods We cultured six cases of high-grade glioma cells from patient's tumor tissues. MTT assay was used to detect cell proliferation and toxicity. Flow cytometry was used to detect cell cycle and apoptosis rate. Specific PCR and immunofluorescence were used to detect the expression of O6-methylguanine-DNA methyltransferase (MGMT) methylation status and MGMT protein respectively. Results MTT assay suggested that compared with the control group, GM-CSF group had increased cell viability in varying degrees. In three cases of cells (MGMT gene methylation), the cell viability of the combination group [(67.67±1.16), (68.13±1.06), (68.42±1.73)]was significantly lower than that of the corresponding TMZ group [(90.00±1.73), (82.33±1.53), (82.67 ±2.11)] (P<0.05). However, there was no significant difference between the two groups in another three cases (MGMT gene unmethylated) (P>0.05). For the MGMT methylation cells, the apoptosis rate in combination group was higher than that in the corresponding TMZ group(P<0.05), which coincided with MTT assay results. In all 6 cases of primary glioma cells, GM-CSF treated group showed significant reduction in the fraction of cells in G1 phase with concomitant increase in S phase(P<0.05). Conclusion GM-CSF could induce high-grade glioma cells entering the cell cycle rapidly, which could enhance the lethal effect of TMZ on glioma cells with MGMT gene promoter methylation.However this effect is not ideal on glioma cells with MGMT unmethylation.
  • [1]
    Khasraw M, Lassman AB. Advances in the treatment of malignant gliomas[J]. Curr Oncol Rep, 2010, 12(1): 26-33.
    [2]
    See SJ, Gilbert MR. Chemotherapy in adults with gliomas[J]. Ann Acad Med Singapore, 2007, 36(5): 364-6.
    [3]
    Weller M. Novel diagnostic and therapeutic approaches to malignant glioma[J]. Swiss Med Wkly, 2011, 141: w13210.
    [4]
    Chamberlain MC, Raizer J. Extended exposure to alkylator chemotherapy: delayed appearance of myelodysplasia[J]. J Neurooncol, 2009, 93(2): 229-32.
    [5]
    George BJ, Eichinger JB, Richard TJ. A rare case of aplastic anemia caused by temozolomide[J]. South Med J, 2009, 102: 974-6.
    [6]
    Revoltella RP, Menicagli M, Campani D. Granulocyte-macrophage colony-stimulating factor as an autocrine survival-growthfactor in human gliomas[J]. Cytokine, 2012, 57(3): 347-59.
    [7]
    Saito Y, Uchida N, Tanaka S, et al. Induction of cell cycle entry eliminates human leukemia stem cells in a mouse model of AML[J]. Nat Biotechnol, 2010, 28(3): 275-80.
    [8]
    Natsurae A, Wakabayashi T, Ishii D, et al. A combination of IFNbeta and temozolomide in human glioma xenograft models: implication of p53 mediated MGMT downregulation[J]. Cancer Chemother Pharmacol, 2008, 61(4): 653-9.
    [9]
    Sielska M, Przanowski P, Wylot B, et al. Distinct roles of CSF family cytokines in macrophage infiltration and activation in glioma progression and injury response[J]. J Pathol, 2013, 230(3): 31 0-21.
    [10]
    Ugur HC, Taspinar M, Llgaz S, et al. Chemotherapeutic resistance in anaplastic astrocytoma cell lines treated with a temozolomide- lomeguatrib combination[J]. Mol Biol Rep, 2014, 41(2): 697-703.
    [11]
    Kohanbash G, McKaveney K, Sakaki M, et al. GM-CSF promotes the immunosuppressive activity of glioma-infiltrating myeloid cells through interleukin-4 receptor-α[J]. Cancer Res, 2013, 73 (21): 6413-23.
  • Related Articles

    [1]XIONG Binghong, MA Li, CHENG Yong, ZHANG Caiquan. Laparoscopic Versus Open Rectectomy for Rectal Cancer: A Meta-analysis of Randomized Controlled Trials on Recurrence and Mortality[J]. Cancer Research on Prevention and Treatment, 2014, 41(01): 46-52. DOI: 10.3971/j.issn.1000-8578.2014.01.011
    [2]GONG Hong-yun, SONG Qi-bin, YAO Yi, HU Qin-yong. A Meta-analysis on Effects of Adjuvant Radiotherapy after Radical Resection of Thymoma[J]. Cancer Research on Prevention and Treatment, 2011, 38(11): 1292-1295. DOI: 10.3971/j.issn.1000-8578.2011.11.019
    [3]CHANG Qing, MAO Yong-rong, WU Chang-ming, WANG Ming-wei. Clinicopathologic Features of 1 Case of Composite Haemangioendothel ioma and Relative Literatures Review[J]. Cancer Research on Prevention and Treatment, 2007, 34(11): 868-870. DOI: 10.3971/j.issn.1000-8578.1409
    [5]Lin Dongmei, . Clinical-pathologic characteristics of Pulmonary balstoma[J]. Cancer Research on Prevention and Treatment, 1997, 24(1): 29-30.
    [6]Li Shenyl, . A CLINICAL AND PATHOLOGIC STUDY OF MALIGNANT MIXED MULLERIAN TUMORS OF THE UTERUS 1958—1988[J]. Cancer Research on Prevention and Treatment, 1991, 18(1): 3-7.
    [7]Chen Xiujian. CLINICOPATHOLGIC ANALYSIS OF CYLINDROMATOUS ADENOCARCINOMA OF MINOR SALIVARY GLAND[J]. Cancer Research on Prevention and Treatment, 1989, 16(2): 100-102.

Catalog

    ZHANG Hui

    1. On this Site
    2. On Google Scholar
    3. On PubMed
    Article views (1845) PDF downloads (553) Cited by()

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return