Effect of inhibiting of HIF-1α and STAT3 combined with irradiation on laryngeal squamous carcinoma cells of xenograft mice / 中国耳鼻咽喉头颈外科

ABSTRACT

OBJECTIVE To investigate theradiosensitization of combined inhibition of signal transducer and activator of transcription 3(STAT3) and hypoxia-inducible factor-1α(HIF-1α)on laryngeal squamous carcinoma of xenograft mice and its underlying mechanisms.METHODS Xenograft mice were divided into 5 groups randomly control group(A), irradiation group(B), irradiation and AG490 group(C), irradiation and PX478 group(D), irradiation combined AG490 and PX478 group(E). The size of xenograft tumor was measured and calculated. The expression of Ki67 and HIF-1α was detected by immunohistochemical method. Western blot was used to detect the expression of PARP1.RESULTS The size of xenograft tumor in group E was smaller compared with that in group C and group D. There were significantly difference between them respectively (t=12.367,11.598,P=0.000). The expression of HIF-1α in group E was lower than that in group C and group D respectively, and there were significantly difference respectively(t=5.422, 3.000,P<0.05). Ki67 index in group E was lower compared with that in group C and group D respectively and there were significantly difference respectively (t=4.479, 4.352,P<0.05). The level of cleaved PARP-1 in group E was higher than that in group C and group D respectively and there were significantly difference respectively (t=5.507, 7.102,P<0.05). CONCLUSION Combined inhibition of STAT3 and HIF-1α can increase the radiosensitivity of human laryngeal squamous carcinoma in the xenograft mice.