Izvorni znanstveni članak
Silencing of Heat Shock Protein 70 Expression Enhances Radiotherapy Efficacy and Inhibits Cell Invasion in Endometrial Cancer Cell Line
Xue-lian Du
; Department of Gynecologic Oncology, Shandond Tumor Hospital, Shandong University, Jinan, People's Republic of China
Tao Jiang
; Department of Gynecologic Oncology, Shandond Tumor Hospital, Shandong University, Jinan, People's Republic of China
Ze-qing Wen
; Depatrment of Obstetrics and Gynecology, Provincial Hospital affiliated to Shandong University, Jinan, People's Republic od China
Rong Gao
; Department of Gynecologic Oncology, Shandond Tumor Hospital, Shandong University, Jinan, People's Republic of China
Min Cui
; Depatrment of Obstetrics and Gynecology, Provincial Hospital affiliated to Shandong University, Jinan, People's Republic od China
Fei Wang
; Depatrment of Obstetrics and Gynecology, Provincial Hospital affiliated to Shandong University, Jinan, People's Republic od China
Sažetak
Aim To investigate the role of heat shock proteins 70
(HSP70) in radiosensitivity and invasiveness of endometrial
cancer in vitro.
Methods HSP70 expression was silenced in relatively radioresistant,
well-differentiated human endometrial cancer
cell line ISK, using small interference RNA method, or by
HSP70 overexpression after transfecting a HSP70-expressing
vector. The effect of HSP70 on ISK cell line response
to irradiation was evaluated. The surviving fraction was
measured using colony-formation assay. Apoptosis was
detected by flow cytometry and HSP70 expression was
determined by quantitative real-time polymerase chain reaction,
western-blot, and/or immuocytochemistry. Cell invasiveness
was measured using transwell invasion assay.
Results HSP70 silencing caused a significant increase in
irradiation-induced cell killing in comparison with control
cells, with an enhancement factor of 1.27, and in the
percentage of apoptotic cells (14.22% vs 6.74%, P = 0.021).
After 4 Gy irradiation, mean ± standard deviation survival
fraction in ISK cells was reduced to 0.32 ± 0.04 in comparison
with control values but in ISK/siRNA-HSP70 cells the
survival fraction was higher and amounted to 0.51 ± 0.08
(P = 0.026). Silencing HSP70 significantly inhibited cell invasion
before and after irradiation (106 ± 19 vs 219 ± 18 and
119 ± 16 vs 256 ± 31, P = 0.007). On the contrary, ectopic
overexpression of HSP70 attenuated irradiation-induced
apoptosis (7.15% vs 4.08%, P = 0.043) and induced more
ISK/HSP70 cells invaded through the filters than mock-infected
cells before and after irradiation (274 ± 21 vs 194 ± 16
before irradiation, and 298 ± 24 vs 227 ± 19 after irradiation,
respectively, P = 0.032).
Conclusion Disruption of HSP70-induced cytoprotection
during irradiation enhances therapeutic effect of irradiation,
which makes HSP70 a promising target in the research
of endometrial cancer.
Ključne riječi
endometrial cancer; Osteopontin (OPN); angiogenesis
Hrčak ID:
38725
URI
Datum izdavanja:
15.4.2009.
Posjeta: 1.323 *