CAFs外泌体通过上调ABCB5诱导乳腺癌细胞化疗耐药 |
| |
引用本文: | 胡晓鹏,张 哲,晏昱婧,罗智勇,吴亚群. CAFs外泌体通过上调ABCB5诱导乳腺癌细胞化疗耐药[J]. 现代生物医学进展, 2018, 0(19): 3637-3641 |
| |
作者姓名: | 胡晓鹏 张 哲 晏昱婧 罗智勇 吴亚群 |
| |
作者单位: | 华中科技大学同济医学院附属同济医院;郑州大学附属第一医院 |
| |
基金项目: | 国家自然科学基金青年基金项目(81502373) |
| |
摘 要: | 目的:探讨肿瘤相关成纤维细胞(CAFs)诱导乳腺癌细胞耐药及其作用机制。方法:从临床样本中分离培养CAFs,获取条件培养基,并纯化外泌体。使用CAFs条件培养基或CAFs外泌体与CD44+的乳腺癌干细胞(CSCs)和CD44-的非干细胞亚群共培养,并用5氟尿嘧啶(5-FU)处理共培养的细胞,通过成球实验和CCK8实验检测细胞的自我更新能力和存活能力。抑制细胞中ABCB5的表达,检测5-FU对细胞存活能力的影响。结果:CAFs条件培养或外泌体处理的CSCs自我更新能力和对5-FU的耐药能力更强,成球能力和对5-FU耐药性上升约1.5-2倍。CAFs外泌体可提高CSCs中ABCB5的表达水平约4-5倍,抑制ABCB5可降低CSCs的耐药性至原来的约60-80%。结论:CAFs通过旁分泌外泌体增强CSCs的自我更新能力并通过上调CSCs中ABCB5的表达水平促进其对化疗药物的抵抗。
|
关 键 词: | 乳腺癌;肿瘤相关成纤维细胞;外泌体;耐药 |
收稿时间: | 2018-05-28 |
修稿时间: | 2018-06-23 |
CAFs-exosomes Induce Chemoresistance of Breast Cancer Cells via Upregulating ABCB5 |
| |
Abstract: | ABSTRACT Objective: To explore drug resistance and its underlying mechanisms of breast cancer cells induced by carcinoma-as- sociated fibroblasts (CAFs). Methods: CAFs were isolated from clinical samples and cultured to produce conditioned medium (CM) fol- lowed by purification of exosomes. Sphere-formation assay and CCK8 assay were performed to detect the capacity of self-renewing and survival of CD44+ breast cancer stem cells (CSCs) and CD44- non-CSCs cocultured with CAFs-CM or exosomes and treated with 5-FU. The survival ability of CSCs was detected after knocking down of ABCB5. Results: Treatment with CAFs-CM or exosomes enhanced the capacity of self-renewing and resistance to 5-FU of CSCs, sphere formation ability and chemoresistance to 5-FU increased about 1.5 to 2 folds. CAFs-exosomes increased the expression of ABCB5 of CSCs to about 4 to 5 folds and knockdown of ABCB5 decreased its drug resistance to 60-80% of that of normal ABCB5 expression groups. Conclusion: CAFs-exosomes enhanced the capacity of self-renewing of CSCs and upregulated the expression of ABCB5 thus contributing to its resistance to chemotherapy. |
| |
Keywords: | Breast cancer Carcinoma-associated fibroblasts Exosomes Drug resistance |
本文献已被 CNKI 等数据库收录! |
| 点击此处可从《现代生物医学进展》浏览原始摘要信息 |
|
点击此处可从《现代生物医学进展》下载免费的PDF全文 |