内分泌及化疗对ER+乳腺癌CD44+CD24-/low细胞亚群的实验与临床研究

目的:探讨内分泌治疗及化疗对雌激素受体(estrogen receptor,ER)阳性的乳腺癌CD44+CD24-/low细胞亚群的影响.方法:用3个浓度的雌二醇(estradiol,E2)和E2+他莫西芬(tamoxifen,TAM)处理乳腺癌MCF-7细胞,用工作浓度的化疗药物(多西他赛、紫杉醇、表柔比星和5-氟尿嘧啶)处理MCF-7细胞,FCM法检测各组细胞中CD44+CD24-/low的细胞比例,并检测ER+的转移性乳腺癌(metastatic breast cancer,MBC)患者化疗前、后外周静脉血中CD45-CD44+CD24-/low的细胞比例.结果:不同浓度E2培养MCF-7细胞10和20 d后,CD44+ CD24-/low细胞比例均高于对照组,E2+TAM组低于相应浓度E2组.各化疗药物作用MCF-7细胞24 h后,CD44+CD24-/low细胞比例均上升；而继续培养至20 d后,CD44+ CD24-/low细胞比例降低.部分缓解和疾病稳定的MBC患者,化疗后外周血CD45-CD44+CD24-/low细胞比例降低；而疾病进展者化疗后外周血CD45-CD44+CD24-/low细胞比例上升.结论:E2促进MCF-7细胞中CD44+CD24-/low细胞亚群的生长,TAM可抑制MCF-7细胞中CD44+CD24-/low细胞亚群的生长；MCF-7细胞中CD44+CD24-/low细胞亚群对多西他赛、紫杉醇、表柔比星和5-氟尿嘧啶均有抵抗能力；化疗有效患者外周血中CD45-CD44+CD24-/low细胞比例降低.

Experimental and clinical research on endocrine therapy and chemotherapy for a subset of CD44+CD24-/low cells of estrogen receptor-positive breast cancer

Objective:To investigate the influence of endocrine therapy and chemotherapy on a subset of CD44+CD24-/low cells of estrogen receptor(ER)-positive breast cancer.Methods:Breast cancer MCF-7 cells were treated with estradiol(E2) of three concentrations,E2 plus tamoxifen(TAM),and docetaxel,paclitaxel(PTX),epirubicin(EPI) and 5-fluorouracil(5-Fu) of working concentration,respectively.The proportion of CD44+CD24-/low cells in each drug-treated group and the proportion of CD45-CD44+CD24-/low cells in peripheral blood of patients with ER+ metastatic breast cancer(MBC) before and after chemotherapy were detected by flow cytometry(FCM).Results:The proportions of CD44+CD24-/low cells after treatment with different concentrations of E2 for 10 d and 20 d were higher than those of the untreated MCF-7 cells,while the proportion of CD44+CD24-/low cells after treatment with E2 plus TAM was lower than that of the CD44+CD24-/low cells treated with E2 at the corresponding concentration.The proportions of CD44+CD24-/low cells after treatment with different chemotherapeutic drugs for 24 h were increased,while decreased after treatment for 20 d.The proportion of CD45-CD44+CD24-/low cells in peripheral blood was decreased in MBC patients achieving partial remission and stable disease after chemotherapy,while increased in MBC patients achieving progressive disease.Conclusion:E2 can promote the proliferation of a subset of CD44+CD24-/low cells derived from MCF-7 cells,but TAM can inhibit this effect.The CD44+CD24-/low cells have resistance to docetaxel,PTX,EPI and 5-Fu.The proportion of CD45-CD44+CD24-/low cells in peripheral blood of patients response to chemotherapy is decreased.