【摘要】 背景:肿瘤干细胞是恶性肿瘤复发及转移的根源,不同治疗方法对肿瘤中肿瘤干细胞的影响是临床研究的重点。目的:探讨内分泌和化疗对乳腺肿瘤患者干细胞的影响。方法:（1）对雌激素受体阳性人乳腺癌细胞株MCF-7进行复苏和培养,选取第3代对数期细胞分为对照组、雌二醇组和雌二醇+三苯氧胺组。对照组培养基中添加等量无水乙醇,雌二醇组分为1×10^-7,1×10^-8,1×10^-9mol/L三个亚组,分别在培养基中加入1×10^-7,1×10^-8,1×10^-9mol/L雌二醇。雌二醇+三苯氧胺组按雌二醇浓度的差异分为三个亚组,培养基中分别加入1×10^-7,1×10^-8,1×10⁽-90mol/L雌二醇,3个亚组均同时加入1×10^-6mol/L的三苯氧胺。（2）晚期复发转移乳腺癌女性患者15例为雌激素受体阳性复发转移乳腺癌组,接受化疗治疗。另取15名健康志愿者作为健康对照组。结果与结论:（1）雌二醇组和雌二醇+三苯氧胺组CD44+CD24-/low细胞亚群比例均显著高于对照组（P<0.05）,雌二醇组CD44+CD24-/low细胞亚群比例显著高于同浓度雌二醇+三苯氧胺组（P<0.05）。各组培养10 d和20 d时的CD44+CD24-/low细胞亚群比例接近（P>0.05）。（2）不同化疗药物均对MCF-7细胞的增殖产生一定的抑制作用,且呈现出剂量-效应依赖现象。MCF-7经不同化疗药物干预24 h后,细胞中CD44+CD24-/low细胞亚群的比例均明显增加（P<0.05）;但干预20 d后仅紫杉醇和阿霉素组细胞中CD44⁺CD24^-/low细胞亚群比例高于对照组（P<0.05）。（3）健康者外周血CD44+CD24-/low细胞亚群比例显著低于雌激素受体阳性复发转移乳腺癌患者（P<0.05）。在15例雌激素受体阳性复发转移乳腺癌患者中,9例疾病稳定,5例部分缓解,1例化疗无效,疾病进展。化疗有效者化疗后的外周血CD45-CD44+CD24-/low细胞亚群比例均显著低于化疗前（P<0.05）。（5）结果说明内分泌治疗与化疗会对雌激素受体阳性乳腺癌的CD44⁺CD24^-/low细胞亚群产生一定的影响。MCF-7细胞中CD44⁺CD24^-/low细胞亚群会对一定的化疗药物产生抵抗能力,经化疗有效的患者外周血CD45-CD44⁺CD24^-/low细胞比例会出现下降。更多还原

【Abstract】 BACKGROUND: Tumor stem cells are the root of cancer recurrence and metastasis, so clinical researches should focus on the effects of different treatments on tumor stem cells.OBJECTIVE: To explore the effects of endocrine therapy and chemotherapy on stem cells in patients with breast cancer.METHODS: After recovery and cultivation of estrogen receptor-positive human breast cancer cell lines MCF-7, passage 3 cells in logarithmic phase were selected and divided into three groups containing control, estradiol and estradiol with tamoxifen groups. The estradiol group was divided into three subgroups: 10^-7, 10^-8and 10^-9mol/L estradiol was added into the medium, respectively; the estradiol with tamoxifen group was divided into three subgroups: 10^-7, 10^-8and 10^-9mol/L estradiol with 10-6mol/L tamoxifen were added into the medium, respectively. The same amount of absolute ethyl ethanol was added into the medium of control group. Fifteen female patients with late recurrence and metastasis of breast cancer received chemotherapy as recurrence and metastasis group. Another 15 healthy volunteers were selected as healthy control group.RESULTS AND CONCLUSION: The proportion of CD44+CD24-/lowcell subsets in the estradiol and estradiol with tamoxifen groups was significantly higher than that of the control group（P < 0.05）, and the proportion of CD44+CD24-/lowcell subsets in the estradiol group was significantly higher than that of the estradiol with tamoxifen group at the same concentration（P < 0.05）. The proportion of CD44+CD24-/lowcell subsets had no significant differences among groups at 10 and 20 days of culture（P < 0.05）. The proportion of CD44+CD24-/lowcell subsets significantly increased in MCF-7 cells after 24-hour intervention with different chemotherapy drugs. But only the proportion of CD44+CD24-/lowcell subsets in the paclitaxel and doxorubicin groups was significantly higher than that of the control group after 20-day intervention（P <0.05）. Besides, the proportion of CD44⁺CD24^-/lowcell subsets in the peripheral blood of healthy volunteers was significantly lower than that of the recurrence and metastasis group（P < 0.05）. Among 15 patients with late recurrence and metastatic of breast cancer, 9 had stable disease, 5 had partial remission, 1 had failed chemotherapy and cancer progression. Moreover, the proportion of CD45^-CD44⁺CD24^-/lowcell subsets in the peripheral blood of patients sensitive for chemotherapy was significantly lower than that before treatment（P < 0.05）. In conclusion, both endocrine therapy and chemotherapy exert a certain effect on the CD44⁺CD24^-/lowcell subsets of breast cancer positive for estrogen receptor. Given that CD44⁺CD24^-/low cell subsets in MCF-7 cells resist chemotherapy drugs, the proportion of CD45^-CD44⁺CD24^-/low cells in the peripheral blood of patients sensitive for chemotherapy is decreased.更多还原