关键词: 低氧诱导因子-1&alpha, 食管肿瘤, 放射敏感性, RNA干扰, 凋亡

Abstract:

OBJECTIVE: To investigate the expression of HIF-1α and EGFR in esophageal squamous carcinoma cell line Eca109 under hypoxia，in order to explore the effect of HIF-1α on radiosensitivity and its possible molecular mechanism. METHODS：CoCl2 was used to mimic hypoxic tumor microenvironment. mRNA levels of HIF-1α and EGFR under hypoxia were detected by reverse transcription-polymerase chain reaction(RT-PCR)，and protein levels were measured by immunohistochemistry. The effect silenced of HIF-1α gene on EGFR expression was assayed by Western blot. Radiosensitivity was evaluated via detection of apoptosis after radiation by flow cytometer (FCM)，and then the effect of silencing HIF-1α on radiosensitivity was measured. RESULTS：Under hypoxia，HIF-1α mRNA had no significant change (P>0.05)，while its protein increased obviously. EGFR mRNA was up-regulated (P<0.05)，and its protein also increased accordingly. The siRNA targeting HIF-1α gene down-regulated HIF-1α in Eca109 cells efficiently under hypoxia，and EGFR protein levels were down-regulated as well (P<0.05). The radiosensitivity in esophageal carcinoma cell line Eca109 was lower under hypoxia than that in normoxia. The siRNA targeting HIF-1α could partially reverse radioresistance. CONCLUSION：Hypoxia could increase HIF-1α protein expression in esophageal squamous carcinoma Eca109 cell. Resistance to radiation enhanced in Eca109 cells maybe correlated with HIF-1α up-regulating the expression of EGFR mRNA and protein levels. Radiosensitivity could be augmented if HIF-1α was effectively suppressed.

Key words: hypoxia inducible factor-1&alpha, esophageal carcinoma, radiosensitivity, RNA interference, apoptosis