Asian Pacific Journal of Cancer Prevention

  • 제15권5호
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  • Pages.2353-2358
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  • 2014
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  • 1513-7368(pISSN)
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  • 2476-762X(eISSN)
아시아태평양암예방학회 (Asian Pacific Journal of Cancer Prevention)
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Influence of Ionizing Radiation on Ovarian Carcinoma SKOV-3 Xenografts in Nude Mice under Hypoxic Conditions

  • Zhang, Yong-Chun (Oncology Department, the Affiliated Hospital of Qingdao University) ;
  • Jiang, Gang (Oncology Department, the Affiliated Hospital of Qingdao University) ;
  • Gao, Han (Pathology Department, Qingdao municipal hospital) ;
  • Liu, Hua-Min (Oncology Department, the Affiliated Hospital of Qingdao University) ;
  • Liang, Jun (Oncology Department, the Affiliated Hospital of Qingdao University)
  • 발행 : 2014.03.01
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초록

Purpose: We aimed to detect the expression of HIF-1${\alpha}$, VEGF, HPSE-1 and CD31 in SKOV3 xenografts in nude mice treated with different doses of ionizing radiation, trying to explore the possible mechanism of hypoxia and radioresistance. Methods: Nude mice bearing SKOV3 xenografts were randomly divided into 4 groups: Group A (control group, no ionizing radiation), Group B (treated with low dose of ionizing radiation: 50cGy), Group C (treated with high dose of ionizing radiation: 300cGy), Group D ( combined ionizing radiation, treated with ionizing radiation from low dose to high dose : 50cGy first and 300cGy after 6h interval). The mRNA levels of HIF-1 and VEGF in each group were detected by real time polymerase chain reaction, while HPSE-1 expression was measured by ELISA. The microvessel density (MVD) and hypoxic cells were determined through immunohistochemical (IHC) staining of CD31 and HIF-1a. Results: Significant differences of HIF-1${\alpha}$ mRNA level could be found among the 4 groups (F=74.164, P<0.001): Group C>Group A>Group D> Group B. The mRNA level of VEGF in Group C was significantly higher than in the other three groups (t=-5.267, P=0.000), while no significant difference was observed among Group A, B and D (t=1.528, 1.588; P=0.205, 0.222). In addition, the MVD was shown to be the highest in Group C (t=6.253, P=0.000), whereas the HPSE-1 level in Group A was lower than in Group B (t=14.066, P=0.000) and higher than in Group C (t=-21.919, P=0.000), and similar with Group D (t=-2.066, P=0.058). Through IHC staining of HIF-1a, the expression of hypoxic cells in Group A was (++), Group B was (+), Group C was (+++) and Group D was (+). Conclusion: Ionizing radiation with lowerdoses might improve tumor hypoxia through inhibiting the expression of HIF-1 and HPSE-1, whereas higherdoses worsen tumor hypoxic conditions by up-regulating HIF-1${\alpha}$, HPSE-1, VEGF and CD31 levels. A protocol of low-dose ionizing radiation followed by a high-dose irradiation might at least partly improve tumor hypoxia and enhance radiosensitivity.

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피인용 문헌

  1. Expression of Hypoxia-inducible Factor Prolyl Hydroxylase 3 HIFPH3 in Human Non-small Cell Lung Cancer (NSCLC) and Its Correlation with Prognosis vol.15, pp.14, 2014, https://doi.org/10.7314/APJCP.2014.15.14.5819
  2. Low-dose radiation may be a novel approach to enhance the effectiveness of cancer therapeutics vol.139, pp.10, 2016, https://doi.org/10.1002/ijc.30235