王耀焓 张培彤 杨栋 韩海英 郭秀伟 祁鑫 张芸

摘要：目的 體内实验观察不同剂量苏木、川芎对肿瘤干细胞样细胞标志物ABCG2的影响。方法 将无血清培养获得的球细胞接种于裸鼠腋下，将裸鼠随机分为对照组、苏木高剂量组、苏木低剂量组、川芎高剂量组和川芎低剂量组，各给药组给予相应药物灌胃，21 d后检测抑瘤率，激光共聚焦、Western blot和RT-PCR分别检测瘤体ABCG2蛋白和mRNA表达。结果 经无血清培养获得的球细胞具有无限增殖、抗凋亡、高表达干细胞标志物等干细胞性能，川芎高、低剂量组可明显抑制瘤体生长（P<0.05），其中川芎低剂量组抑瘤率明显高于川芎高剂量组，苏木高、低剂量组虽对瘤体有一定的抑制作用，但差异无统计学意义（P>0.05）；与对照组比较，川芎低剂量组可明显抑制ABCG2蛋白的表达，苏木高、低剂量组对ABCG2蛋白表达均无抑制作用，除川芎低剂量组外，各给药组对ABCG2 mRNA表达均有上调作用。结论 低剂量川芎可能通过抑制肿瘤干细胞标志物ABCG2蛋白的表达，靶向杀伤肿瘤干细胞。

关键词：苏木；川芎；肿瘤干细胞；ABCG2蛋白

DOI：10.3969/j.issn.1005-5304.2017.08.014

中图分类号：R285.5 文献标识码：A 文章编号：1005-5304（2017）08-0060-06

Effects of Sappan Lignum and Chuanxiong Rhizoma on Expression of ABCG2 Protein of PG-BE1 Stem Like Cells in Vivo WANG Yao-han， ZHANG Pei-tong， YANG Dong， HAN Hai-ying， GUO Xiu-wei， QI Xin， ZHANG Yun （Department of Oncology， Guanganmen Hospital， China Academy of Chinese Medical Sciences， Beijing 100053， China）

Abstract： Objective To observe the effects of different doses of Sappan Lignum and Chuanxiong Rhizoma on tumor stem cells marker ABCG2 in vivo. Methods Sphere cells obtained from serum culture were inoculated in nude mouse armpit， which were randomly divided into 5 groups： control group， Sappan Lignum high- and low-dose groups， and Chuanxiong Rhizoma high- and low-dose groups. Each medication group was given relevant medicine for gavage. 21 days later， inhibition tumor rate and ABCG2 protein and mRNA expression were detected with confocal microscope， Western blot， and RT-PCR. Results The sphere cells obtained from serum free culture had the abilities of cancer stem cells， such as proliferation， anti-aptosis and high expression of cancer stem cells markers. Chuanxiong Rhizoma high- and low-dose groups could inhibit tumor growth （P<0.05）， and the inhibitory rate of Chuanxiong Rhizoma low-dose group was higher than the Chuanxiong Rhizoma high-dose group. Sappan Lignum high- and low-dose groups inhibited tumor growth without statistical significiance （P>0.05）. Compared with the control group， Chuanxiong Rhizoma low-dose group could significantly inhibit the expression of resistant protein of ABCG2. Sappan Lignum high- and low-dose groups could not inhibit the protein expression of ABCG2. Each medication group up-regulated the mRNA expression of ABCG2 except for Chuanxiong Rhizoma low-dose group. Conclusion Low dose of Chuanxiong Rhizoma can inhibit the expression of ABCG2 protein levels， which can be the targeting killer for cancer stem cells.

Key words： Sappan Lignum； Chuanxiong Rhizoma； cancer stem cells； ABCG2 protein

基金项目：国家自然科学基金（81173450）

通讯作者：张培彤，E-mail：zhangpeitong@sohu.com

化疗在改善肿瘤患者生存质量、提高患者生存率方面起到重要作用。然而，化疗耐药的存在一直制约着临床疗效的发挥。有研究显示，经化疗后再复发或发生远处转移的乳腺癌患者，大约40%是由于化疗耐药引起的[1]。因此，寻找可以增强化疗敏感性的药物是目前面临的挑战。近几年来，肿瘤干细胞理论的提出对化疗耐药的治疗提出了新的理念。该理论认为，肿瘤干细胞具有自我更新、多向分化、化疗耐药等性能，是肿瘤复发及转移的主要原因。……