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目的:了解人鼻咽低分化鳞癌细胞株HNE1及其耐药株HNE1/DDP的放射敏感性,探讨顺铂(DDP)对耐药株及其亲本细胞株放射增敏的差别,并初步研究吉西他滨对HNE1/DDP的放射增敏作用及其机制。方法:实验分为单纯照射组和照射加药组,应用克隆形成方法,观察单纯照射和照射加药物(DDP或吉西他滨)对细胞的杀伤作用,用Radiomed软件进行曲线拟合作图。免疫组织化学、末端脱氧核苷酰转移酶法(TUNEL法)和流式细胞法观察吉西他滨对耐药细胞株的影响。结果:DDP对HNE1和HNE1/DDP的放射增敏比分别为1.2015和0.9418,而吉西他滨对HNE1/DDP的放射增敏比为1.3791。吉西他滨作用后耐药细胞凋亡增加,bax表达上调,p53没有明显变化,药物作用前后Bcl-2表达均呈阴性,并且使肿瘤细胞周期阻滞在G1期,而S期细胞比例则明显减少。结论:鼻咽低分化鳞癌细胞株HNE1对DDP和放射线没有交叉抵抗。DDP对HNE1具有放射增敏作用,但是对HNE1/DDP无放射增敏作用,而吉西他滨对HNE1/DDP有放射增敏作用,其增敏机制可能与吉西他滨使细胞周期阻滞在G1/S期,以及细胞p53、bax和Bcl-2基因表达变化导致凋亡增加有关。
OBJECTIVE: To investigate the radiosensitivity of HNE1 and HNE1 / DDP cells in human nasopharyngeal poorly differentiated squamous cell carcinoma cell line HNE1 and explore the possible difference of radiosensitization between cisplatin (DDP) and drug resistant strains and their parental cell lines Radiosensitization of gemcitabine on HNE1 / DDP and its mechanism. Methods: The experiment was divided into simple irradiation group and irradiation plus drug group. The killing effect on cells was observed by the method of clone formation and irradiation alone and irradiation plus drug (DDP or gemcitabine). The curve fitting was performed by Radiomed software. Immunohistochemistry, terminal deoxynucleotidyl transferase (TUNEL) and flow cytometry were used to observe the effect of gemcitabine on drug-resistant cell lines. RESULTS: The radiosensitivities of DDP to HNE1 and HNE1 / DDP were 1.2015 and 0.9418, respectively. The radiosensitization ratio of gemcitabine to HNE1 / DDP was 1.3791. Gemcitabine increased the apoptosis of drug-resistant cells, increased the expression of bax, and had no significant change in p53. The expression of Bcl-2 was negative before and after drug treatment, and the cell cycle arrest was at G1 phase, while the percentage of S phase cells was significantly decreased. CONCLUSION: HNE1 is not cross-resistant to DDP and radiation in nasopharyngeal poorly differentiated squamous cell carcinoma cell line. DDP had a radiosensitizing effect on HNE1, but no radiosensitizing effect on HNE1 / DDP, while gemcitabine had a radiosensitizing effect on HNE1 / DDP. Its mechanism of sensitization may be related to the fact that gemcitabine blocks cell cycle arrest in G1 / S phase, As well as the change of p53, bax and Bcl-2 gene expression leading to the increase of apoptosis.