顺铂联合X射线照射人鼻咽癌裸小鼠移植瘤生物效应的实验研究

Radiosensitizing effect of cisplatin on CNE-1 xenograft in nude mice

目的探讨顺铂联合x射线照射对鼻咽高分化鳞癌（CNE-1）裸鼠移植瘤抑瘤率和CyclinB1、CyclinD，转录水平的影响。方法建立CNE-1裸鼠移植肿瘤模型后随机分成对照、顺铂、急速照射、模拟调强放疗（IMRT）和模拟IMRT加顺铂组，照射剂量为单次20Gy，顺铂剂量为15μg／g体重。绘制肿瘤生长曲线，计算肿瘤抑制率，并用RT—PCR方法测定各组肿瘤组织中CyclinB1、CyclinD1的转录水平。组间比较行单因素方差分析。结果对照、顺铂、急速照射、模拟IMRT和模拟IMRT加顺铂组肿瘤抑制率分别为-129．1％、-71．2％、42．5％、35．3％和47．1％[急速照射与模拟IMRT组不同（P=0．034），但急速照射与模拟IMRT加顺铂组相似（P=0．222）]；CyclinB，转录水平分别为0．429、0．386、0．322、0．354和0．268[急速照射与模拟IMRT组、模拟IMRT加顺铂组均不同（P=0．007、0．000）]；CyclinD1转录水平分别为0．716、0．583、0．348、0．495和0．296[急速照射与模拟IMRT组不同（P=0．000），但急速照射与模拟IMRT加顺铂组相似（P=0．072）]。结论20Gy单次x射线照射和加顺铂均能缩小肿瘤体积，但单用顺铂仅能延缓生长；20Gy单次X射线照射和加顺铂以及单纯顺铂均可致CyclinB1、CyclinD1转录水平下调；而模拟IMRT因时间延长可使肿瘤抑制率下降和CyelinB1、CyclinD1下调减弱，但联合顺铂后或许能补偿这种降低效应。

Objective To investigate influence of cisplatin （DDP） on the tumor inhibition rate, transcriptional levels of CyclinB1 and CyclinD1 of CNE-1 xenograft in nude mice. Methods Tumor mode of nude mice CNE-1 xenograft was established. Then mice were divided into control arm, DDP arm, high speed irradiation arm, simulated intensity modulated radiation therapy （IMRT） arm and simulated IMRT ＋ DDP arm,with 12 mice in each arm. Irradiation dose was 20 Gy with a single fraction. DDP was 15 μg/g weight. The maximum diameter of tumor base was measured every other day. The growth curve was drawn and tumor inhibition rate werevcalculated after 40 days. The transcriptional level of CyclinBl and CyclinD1 of xenograft was measured by RT-PCR. The results of different groups were compared with one-factor analysis of variance. Results Tumor inhibition rates of the control arm, DDP arm, high speed irradiation arm, simulated IMRT arm and simulated IMRT ＋ DDP arm were - 129.1% , -71.2% , 42. 5% , 35.3% and 47. 1%, respectively. There was significant difference between the high speed irradiation arm and simulated IMRT arm （ P = 0. 034 ） , but not between the high speed irradiation arm and simulated IMRT ＋ DDP arm （P =0. 222）. The transcriptional levels of CyelinB1 in the arms were 0. 429, O. 386, 0. 322, 0. 354 and 0. 268. There were significant differences between the high speed irradiation arm and the simulated IMRT arm or the simulated IMRT ＋ DDP arm （ P = 0. 007 and 0. 000 ） . The transcriptional levels of CyclinD1 in the arms were 0. 716, 0. 583, 0. 348, 0. 495 and 0. 296, respectively. There was significant difference between the acute irradiation arm and the simulated IMRT arm （ P = 0. 000 ）, but there was no significant difference between the high speed irradiation arm and the simulated IMRT ＋ DDP arm （ P = 0. 072 ）. Conclusions Irradiation of 20 Gy single fraction, or combined with DDP are effective on the CNE-1 xenograft in nude mice, but DDP alone can only lower the tumor growth speed. Irradiation of 20 Gy single fraction,or combined with DDP, or DDP alone can reduce the transcriptional levels of CyclinB1 and CyclinDl. As the single therapeutic time is prolonged in IMRT mode, the tumor inhibition rate is reduce, and the reduce of the transcriptional levels of CyclinB1 and CyclinD1 is depressed, while combined DDP can compensate the decline of the biological effect.