Author of

• 13580

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  P1.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 233)

  • Event: WCLC 2015
  • Type: Poster
  • Track: Biology, Pathology, and Molecular Testing
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)

  • 13686

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    P1.04-106 - Granulocyte Colony-Stimulating Factor Enhances the Anticancer Effects of Cisplatin Against Lung Cancer by Promoting Angiogenesis (ID 1027)

    09:30 - 09:30  |  Author(s): Y. Ohno
    • Abstract

    Background:
    G-CSF is a hematopoietic growth factor which enhances the proliferation and differentiation of neutrophil precursor cells. However the results of studies on G-CSF-induced tumor growth are controversial. Recently, some studies reported that G-CSF stimulates the growth of tumor cells such as colon cancer cells, small lung cancer cells , skin carcinoma cells and astrocytoma cells, In contrast, Brandstetter et al. reported that G-CSF does not exhibit any effect on the proliferation of ovarian carcinoma cell lines or tumor samples despite presence of the G-CSF receptor in the tested cell lines and biopsies.
    
    Methods:
    In vitro effects of G-CSF on tumor cell proliferation. Two mouse non-small lung cancer cell lines, Lewis lung cancer cell line (LL-2) and KLN-205 were grown in DMEM medium with FBS. In vivo evaluation of the effects of G-CSF on tumor growth. Seven week-old male C57BL/6 mice were purchased from CLEA Japan . LL-2 cancer cells were grown in culture, harvested and subcutaneously injected as a suspension into the C57BL/6 mice in the proximal dorsa midline. The mice were randomized into 4 groups, group 1) saline control, 2) G-CSF alone, 3) CDDP alone and 4) CDDP plus G-CSF group. The mice were injected 5 mg/kg CDDP intraperitoneally 2 hours after tumor cell transplantation and then, were given 5 mg/kg CDDP intraperitoneally each week. Two hours after CDDP or saline injection, the mice were given 30 mg/kg G-CSF or the same volume of saline intraperitoneally each day, and 21 days after tumor cell transplantation they were sacrificed and the tumors were removed.
    
    Results:
    We found that LL-2 and KLN-205 cell proliferation was unchanged significantly in the presence of various concentrations of G-CSF. To ensure that the results were due to the absence of the G-CSF receptor,we investigated the G-CSF receptor mRNA in these two cell lines by RT-PCR.Groups of mice were intraperiotoneally given 5mg/kg CDDP or saline per week starting 2 hours after tumor cell transplantation. Then, 2 hours after CDDP or saline injection the mice were intraperitoneally given 30m g/kg G-CSF or saline per day. Tumor growth was markedly inhibited in the CDDP and CDDP+G-CSF treatment group compared with the saline control group. Concurrent administration of G-CSF significantly enhanced the tumor suppressing effect of CDDP in early stage tumor growth. 7 days after tumor cells transplantation, the tumor volume were 6.84±9.07 for CDDP plus G-CSF treatment VS 16.34±10.29 mm3 for CDDP alone (p=0.047).
    
    Conclusion:
    In summary, our results provide evidence that G-CSF as a growth factor does not promote tumor cell proliferation. Concurrent (Combination) administration of G-CSF significantly enhances the tumor suppressing effect of CDDP in early stage tumor growth. Thus, concurrent (combination) administration of G-CSF with anticancer agents is a safe and effective method for reducing chemotherapeutic agent-induced myelosuppression. In spite of further studies are required to determine whether this effect of G-CSF is a common feature against lung cancer and the solid tumors of the other organs, in this time, our study suggested a novel importance of G-CSF treatment against cancer therapy.