口腔鳞状细胞癌体内生长的昼夜生物节律特征

Circadian rhythm of oral squamous cell carcinoma in vivo

摘要:

目的：探讨口腔鳞状细胞癌体内生长的昼夜生物节律改变特征。方法：32只裸鼠置于12 h光照、12 h黑暗交替的环境中，将人颊鳞状细胞癌BcaCD885细胞接种于裸鼠颊部，建立颊鳞状细胞癌模型，3周后在24 h内，按灯亮后4、10、16、22 h 4个时间点分别处死8只裸鼠时间以开灯后的小时数为参考（hours after light onset，HALO），即4 HALO、10ＨＡＬＯ、16ＨＡＬＯ、22HALO。取出肿瘤测量体积，用流式细胞仪测定肿瘤细胞的增殖指数（proliferation index，PI）和凋亡指数（apoptosis index，AI）。用余弦分析法检验肿瘤体积、肿瘤细胞PI和AI是否具有昼夜节律性，用方差分析各指标在4个时间点差异的显著性。结果：肿瘤体积和肿瘤细胞PI具有明显的昼夜节律变化特征，肿瘤体积在不同时间点的差异具有统计学意义，肿瘤体积的峰值和谷值分别出现在3.23HALO、15.23HALO，肿瘤细胞PI的峰值和谷值分别出现在6.60HALO、18.16HALO。肿瘤细胞的AI无昼夜节律性，但在不同时间点差异具有统计学意义。结论：体内生长的口腔鳞状细胞癌的细胞增殖活性和肿瘤体积具有昼夜节律变化特点，肿瘤体积和细胞AI在昼夜不同时间点差异变化较大。

Abstract:

Objective：To investigate the change of circadian rhythm in oral squamous cell carcinoma（OSCC）in vivo. Methods：Totally 32 nude mice were maintained in 12 h light alternating with 12 h dark. Human oral squamous cell carcinoma cell line BcaCD885 was transplanted subcutaneously into nude mice cheeks to develop an OSCC animal model. Mice were sacrificed at 4 different time points 4，10，16，22 h（4 hours after light onset（HALO），10HALO，16HALO，22HALO） of 24 h 3 weeks after transplantation，with 8 mice of each group. Tumors were dissected away and tumor sizes were measured. Tumor cell proliferation index（PI） and apoptosis index（AI） were determined by flow cytometry. Cosine analysis was used to detect circadian rhythm of tumor size，tumor cell PI and AI. Vari－ance of significant difference in the four time groups was tested by ANOVA. Results：Tumor size and tumor cell PI exhibited signifi－cant circadian rhythm. Tumor sizes had significant differences at indifferent time points. Peak and trough values of tumor size appeared at 3.23HALO and 15.23HALO，respectively. Peak and trough values of tumor cell PI appeared at 6.60HALO and 18.16HALO，respec－tively. AI of tumor cells showed no circadian rhythm，but the differences of different time points were significant. Conclusions：Cell proliferation and tumor size of OSCC in vivo show circadian rhythm. Tumor size and AI have significant differences at different time points.