Various doses of fractioned irradiation modulates multidrug resistance 1 expression differently through hypoxia-inducible factor 1α in esophageal cancer cells

• Published in: Diseases of the esophagus Vol. 24; no. 7; pp. 481 - 488
• Main Authors: Zhang, G-J., Gao, R., Wang, J-S., Fu, J-K., Zhang, M-X., Jin, X.
• Format: Journal Article
• Language: English
• Published: Malden, USA Blackwell Publishing Inc 01.09.2011
• Subjects: ATP-Binding Cassette, Sub-Family B, Member 1 - biosynthesis; ATP-Binding Cassette, Sub-Family B, Member 1 - radiation effects; Cell Line, Tumor; Dose Fractionation; esophageal cancer; Esophageal Neoplasms - metabolism; Esophageal Neoplasms - radiotherapy; HIF1α; Humans; Hypoxia-Inducible Factor 1, alpha Subunit - physiology; MDR1; radiation; siRNA
• ISSN: 1120-8694; 1442-2050
• DOI: 10.1111/j.1442-2050.2010.01168.x

SUMMARY To evaluate the effect of different regimen of radiotherapy on multidrug resistance 1 (MDR1) expression and analyze the role hypoxia‐inducible factor 1α (HIF1α) played in the whole process. Fifty‐four cell lines established from 96 esophageal cancer biopsy samples were given various doses of fractioned irradiation. The mRNA and protein levels of HIF1α and MDR1 post‐irradiation were measured by quantitative reverse transcription–polymerase chain reaction and Western blot analysis, respectively. HIF1α–siRNA was used to verify the effect of HIF1α on radiation‐mediated MDR1 modulation. In esophageal cancer cells surviving 28 Gy irradiation (2 Gy/f, 14 fractions), MDR1 mRNA expression increased 65.27 ± 5.58%, and HIF1α was elevated by 27.21 ± 2.25%. Interestingly, their expression decreased by 54.38 ± 11.53% and 32.08 ± 4.75% after 7 Gy irradiation (0.5 Gy/f, 14 fractions). HIF1α expression showed a positive correlation with MDR1 expression in the whole process (P < 0.05). Silencing of HIF1α decreased MDR1 expression and blocked changes in MDR1 and HIF1α expression induced by fractioned irradiation. These results indicate that MDR1 is differentially modulated by different doses of fractionated radiation, which should be taken into account when combining radiotherapy and chemotherapy for patients with esophageal cancer.