Heparanase promotes radiation resistance of cervical cancer by upregulating hypoxia inducible factor 1.
Heparanase (HPSE1) is elevated in various types of cancers including cervical cancer, and correlated with poor prognosis. Current study is to investigate the effects of HPSE1 on radiation response in cervical cancer. Colony formation assays after radiation were performed to compare the radiation response among control, HPSE1 knockdown and HPSE1 overexpression HeLa cells. The mRNA and protein levels of HIF1, bFGF and VEGF were measured as indicators for the activity of HIF1 pathway. Xenograft mouse model were used to study the HPSE1 radiation regulator effectsin vivo. Microvessel densities (MVD) were measured in xenograft tumor samples. The survival fractions were significantly lower in HPSE1 knockdown cells and higher in HPSE1 overexpression cells compared with control cells. The mRNA and protein levels of HIF1, VEGF and bFGF are decreased in HPSE1 knockdown cells and increased in HPSE1 overexpression cells. HIF1 inhibition eliminated the radiation protection effects by HPSE1 overexpression. Our results demonstrate HPSE1 is an important regulator of radiation response bothin vivoandin vitro. Further studies are warranted to determine the underlie mechanism of how HPSE1 regulate HIF1 activity and the clinical effects of HPSE1 inhibitors in cervical cancer.
Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University Xi'an 710032, Shaanxi, China.
Jianping
J
Li
Department of Ultrasound, Xijing Hospital, Fourth Military Medical University Xi'an 710032, Shaanxi, China.
Xin
X
Meng
Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University Xi'an 710032, Shaanxi, China.
Jing
J
Hu
Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University Xi'an 710032, Shaanxi, China.
Ying
Y
Zhang
Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University Xi'an 710032, Shaanxi, China.
Yunzhi
Y
Dang
Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University Xi'an 710032, Shaanxi, China.
Lichun
L
Wei
Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University Xi'an 710032, Shaanxi, China.
Mei
M
Shi
HIF1; Heparanase; VEGF; cervical cancer; radiation sensitivity