Influence of Ionizing Radiation on Ovarian Carcinoma SKOV-3 Xenografts in Nude Mice under Hypoxic Conditions

Zhang, Yong-Chun; Jiang, Gang; Gao, Han; Liu, Hua-Min; Liang, Jun

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자료유형: 학술저널

저자정보: 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)

저널정보: 아시아태평양암예방학회 Asian Pacific journal of cancer prevention : APJCP Asian Pacific journal of cancer prevention : APJCP 제15권 제5호

발행연도: 2014.1

수록면: 2,353 - 2,358 (6page)

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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.

#Ionizing radiation #hypoxia inducible factor 1 #vascular endothelial growth factor #CD31 #HPSE-1

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