目的： 探讨小白菊内酯（parthenolide，PTL）对小鼠乳腺癌肿瘤干细胞（cancer stem cell，CSC）的杀伤作用，为临床应用PTL治疗乳腺癌提供实验依据。 方法： 采用5-氟尿嘧啶（5-fluorouracil, 5-FU）化疗法制备富含CSC的小鼠4T1细胞乳腺癌模型，随机分为对照组、5-FU组、PTL组。4周后脱颈处死小鼠，检测各组小鼠肿瘤的体积和重量，流式细胞术检测小鼠肿瘤组织中CD44+CD24-/low细胞比例，Hoechst33342染色法检测侧群（side population，SP）细胞的比例，免疫组化法检测CD55和乙醛脱氢酶1（aldehyde dehydrogenase1，ALDH1）蛋白的表达，倒置显微镜观察乳腺癌细胞微球体的形成。 结果： 成功制备富含CSC的小鼠乳腺癌细胞移植瘤模型，PTL可下调小鼠肿瘤组织中CD44+CD24-/low细胞的比例\[（42.5±3.7）% vs （68.7±32）%，P<0.05\]，有效降低荷瘤小鼠肿瘤组织中SP细胞的比例\[（39.2±1.8）% vs （61.3±2.6）%，P<0.05\]，下调小鼠移植瘤组织中CD55和ALDH1蛋白的表达\[（18.9±1.5）% vs （30.1±1.3）%，（8.1±2.3）% vs （18.0±1.4）%；均P<0.05\]，抑制小鼠肿瘤细胞在无血清培养条件下形成微球体，并可抑制小鼠移植瘤的体积和重量\[（0.625±0.159）cm3 vs （1.715±0184）cm3，（1.467±0.373）g vs （3.367±0.398）g；均P<0.05\]。 结论： PTL在荷瘤小鼠体内可以明显降低肿瘤组织CSC含量，提示PTL可用来靶向杀伤乳腺癌CSC。

Objective:To investigate the effects of parthenolide (PTL) on cancer stem cells (CSCs) of mouse breast cancer in vivo, providing an experimental basis for the clinical treatment of breast cancer with PTL. Methods: The mouse breast cancer model which enriching for 4T1 breast cancer CSCs was established by chemotherapeutic drug 5-fluorouracil (5-FU). Tumor-bearing mice were randomly divided into three groups, a control group, a 5-FU group and a PTL group. Four weeks later, the mice were sacrificed. The mouse tumor volume and weight were measured. Flow cytometry (FCM) was used to measure the proportion of CD44+CD24-/low cells in different tumor tissues; Hoechst 33342 staining was used to measure the proportion of SP (side population) cells; and the expressions of ALDH1 (aldehyde dehydrogenase1) and CD55 proteins were detected by immunohistochemistry. The formation of mammosphere was observed under an inverted microscope. Results: The mouse breast cancer transplanted model enriching for 4T1 breast cancer CSCs was successfully prepared. PTL could significantly reduce the proportion of CD44+CD24-/low cells in the mouse transplanted tumor tissues （\[42.5±3.7\]% vs \[687±3.2\]%，P<0.05), decrease the percentage of the SP cells in mouse transplanted tumor tissues （\[39.2±18\]% vs \[61.3±2.6\]%，P<0.05), and inhibit the expressions of CD55 and ALDH1 proteins in the mouse tumor tissues （\[18.9±1.5\]% vs \[30.1±1.3\]%，\[8.1±2.3\]% vs \[18.0±1.4\]%; all P<0.05). PTL inhibited the formation of mammosphere generated from the mouse tumor 4T1 cells culturing in serum-free medium and the growth of the mouse transplanted tumor (\[0.625±0.159\]cm3 vs \[1.715±0.184\] cm3, \[1.467±0.373\]g vs \[3.367±0.398\] g; P<0.05\]. Conclusion: PTL can significantly reduce the CSC contents in mouse tumor tissues in vivo, which suggests that PTL could be used to target the breast cancer CSC.

河北省自然科学基金资助项目(No. H2012206135)；邢台市科技计划资助项目（No.2012ZC085）