文峰 杨俊 向燕

[摘要] 目的 研究紫杉醇對肝癌细胞恶性生物学行为作用及其MicroRNA-544表达的影响。方法 选取60只昆明小鼠随机分为对照组、模型组和实验组3组，每组20只，对照组为未处理小鼠，模型组为肝癌模型组，实验组为肝癌模型紫杉醇干预组。检测3组小鼠肝细胞或肝癌细胞不同培养周期MicroRNA-544的表达，以及模型组和实验组小鼠肝癌细胞凋亡形态和凋亡率。结果 相同浓度紫杉醇不同作用时间对模型小鼠肝癌细胞的抑制无统计学差异，随着紫杉醇浓度的提升，小鼠的抑癌率显著升高（F组别=4.86，P<0.001）。对照组肝细胞不同培养时间MicroRNA-544表达量的差异无统计学意义（P>0.05）;模型组从第10周开始MicroRNA-544表达量显著下降，第10～22周MicroRNA-544表达量相对稳定;实验组加入紫杉醇开始培养（0周）时肝癌细胞的MicroRNA-544表达量与同期模型组比较差异无统计学意义（P>0.05），随着培养时间的延长，实验组的MicroRNA-544表达量显著上调（F时间=65.37，P<0.001），并且实验组的MicroRNA-544表达量明显高于模型组（F组别=1.83，P<0.05）。与模型组相比较，实验组G0/G1、S期细胞比例显著下降，G2/M期细胞显著上升（F周期=3.47，P<0.001;F组别=95.85，P<0.001），实验组肝癌细胞的凋亡率显著升高（F组别=66.32，P<0.001）。结论 紫杉醇可以抑制肝癌细胞增殖分化并提高其凋亡率，其机制可能与MicroRNA-544表达上调有关。

[关键词] 紫杉酚;肝肿瘤;细胞增殖;微RNAs;昆明小鼠

[中图分类号] R282.71;R735.7  [文献标志码] A  [文章编号] 2096-5532（2020）02-0225-04

doi：10.11712/jms.2096-5532.2020.56.064 [开放科学（资源服务）标识码（OSID）]

[网络出版] http：//kns.cnki.net/kcms/detail/37.1517.R.20200417.0915.007.html;2020-04-17 17：05

[ABSTRACT] Objective To investigate the effects of paclitaxel on the malignant biological behavior and MicroRNA-544 expression of hepatoma cells.  Methods Sixty Kunming mice were randomly divided into control group （no intervention）， model group （establishing a mouse model of hepatocellular carcinoma）， and experimental group （establishing a model of hepatocellular carcinoma+paclitaxel intervention）， with 20 mice in each group. The MicroRNA-544 expression of the hepatocytes or hepatoma cells of the three groups was measured at different culture cycles. The apoptotic morphology and apoptosis rate of hepatoma cells were recorded in the model group and experimental group.  Results The tumor inhibition rate of mice significantly increased with the concentration of paclitaxel （Fgroup=4.86，P<0.001）， but showed no significant differences between different durations of action of paclitaxel at a certain concentration. The control group exhibited no significant differences in the MicroRNA-544 expression of hepatocytes between different culture time points （P>0.05）. The model group displayed significantly decreased expression of MicroRNA-544 from week 10 and then a relatively stable expression level during weeks 10-22. Compared with the model group， the experimental group showed no significant difference in the MicroRNA-544 expression of hepatoma cells at the start of paclitaxel treatment （week 0） （P>0.05）; but the expression level in the experimental group significantly increased with the culture time （Ftime=65.37，P<0.001）， and significantly exceeded that in the model group （Fgroup=1.83，P<0.05）. Compared with the model group， the experimental group had significantly lower percentages of G0/G1-phase and S-phase cells and a significantly higher percentage of G2/M-phase cells （Fcycle=3.47，P<0.001;Fgroup=95.85，P<0.001）， as well as a significantly higher apoptosis rate of hepatoma cells （Fgroup=66.32，P<0.001）.  Conclusion Paclitaxel can inhibit the proliferation and differentiation of hepatoma cells and improve the apoptosis rate， which may be related to the up-regulation of MicroRNA-544 expression.

[KEY WORDS] paclitaxel; liver neoplasms; cell proliferation; MicroRNAs; Kunming mice

肝癌是全球第三大癌症相关性死因疾病，中国的肝癌病人约占世界的55%，且其发病率呈现逐年上升趋势[1-3]。目前肝癌的治疗主要采取手术治疗，但手术后病人的生存率并不理想，对大多数病人特别是晚期病人术后的化疗方案的选择至关重要[4-6]。紫杉醇被认为是目前最为优秀的抗癌天然药物，能够显著抑制多种癌细胞的生长增殖[6-9]，包括肝癌细胞 [10]，但对紫杉醇作用机制的相关研究并不多见。在肝癌进展的过程中，MicroRNA-544可以通过抑制肝癌细胞的增殖并促进其凋亡，进而抑制肿瘤的增殖和生长[11-12]。然而……