[Effect of fractioned irradiation on HIF-1alpha and MDR1 expression in esophageal cancer cells].
OBJECTIVE
To examine the effect of fractioned ionizing radiation on the expression of hypoxia inducible factor-1alpha (HIF-1alpha) and multidrug resistance (MDR1) in human esophageal cancer cells.


METHODS
The mRNA and protein levels of HIF-1alpha and MDR1 in esophageal caner EC9706 cells incubated in the presence of 150 micromol/L CoCl(2) were measured before and after the irradiation by quantitative RT-PCR and Western blotting, respectively. The chemosensitivity and radiosensitivity of the cells were analyzed by MTT assay and clone formation assay.


RESULTS
MDR1 and HIF1alpha expressions were significantly up-regulated in the cells following hypoxia or irradiation (P<0.05). The surviving cell fraction in the exclusive irradiation group was significantly lower than that irradiation+hypoxia group (P<0.05). Compared with exclusive hypoxia group, MDR1 and HIF1alpha expressions were decreased significantly in irradiation+hypoxia group (P<0.05). HIF1alpha expression showed a positive correlation to MDR1 expression (P<0.01).


CONCLUSIONS
Hypoxia is an important factor to induce resistance to chemo- and radiotherapy. Low-dose fractioned irradiation can lower MDR1 and HIF1alpha expressions in esophageal cancer cells, which should be considered when combining radiotherapy chemotherapy for esophageal cancer patients.
Gao
Rui
R
Department of Nuclear Medicine, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China. jacky_mg@163.com
Zhang
Guang-jian
GJ
Fu
Jun-ke
JK
Jin
Xin
X
Zhang
Ming-xin
MX
Li
Fen
F
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000532:radiotherapy; D045744:Cell Line, Tumor; D019583:Dose Fractionation, Radiation; D004938:Esophageal Neoplasms / Q000473:pathology* / Q000532:radiotherapy; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011839:Radiation, Ionizing
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger