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癌症干细胞样细胞导致食管鳞状细胞癌对紫杉醇耐药。

Cancer stem-like cells contribute to paclitaxel resistance in esophageal squamous cell carcinoma.

作者信息

Shen Yanru, Yang Lihui, Li Lei

机构信息

Department of Gastroenterology, Fukang Hospital Affiliated to Tibet University Lhasa, China.

Department of Science and Education, People's Hospital of Tibet Autonomous Region, Tibet University Lhasa, China.

出版信息

Int J Clin Exp Pathol. 2022 Apr 15;15(4):183-190. eCollection 2022.

Abstract

OBJECTIVE

To examine the role of esophageal squamous cell carcinoma (ESCC) stem cells in paclitaxel resistance through the molecular characterization of ESCC stem cells.

METHODS

A resistant cell line (RR-ECl09) of cells were established using intermittent induction and time increments of high-dose paclitaxel in a human esophageal squamous cell carcinoma line (EC109). The multidrug resistance of RR-ECl09 cells to anticancer agents was evaluated by MTT assay. The RR-EC109 and EC109 cells were used for sphere formation assays, clonogenicity assays, stem cell gene expression, and the expression of epithelial-mesenchymal transition markers.

RESULTS

The RR-EC109 cells were established over 7 months. RR-ECl09 cells had 67.258 fold resistance to paclitaxel. The percentage of sphere formation and clone proliferation ability of RR-EC109 cells was higher than that of EC109 cells (P < 0.05). The amount of side population cells in RR-EC109 cells was higher than that of EC109 cells (P < 0.05). RR-EC109 cells produced more mRNA for Bmi1, Nanog, Oct4, Sox2, ABCG2, Nestin, and Ki-67 than EC109 cells (P < 0.05). E-cadherin expression was lower in RR-EC109 cells than in EC109 cells, while N-cadherin, Snail, and Twist expressions were higher in RR-EC109 cells than in EC109 cells (P < 0.05).

CONCLUSIONS

Cancer stem cell (CSC)-like cells exist among paclitaxel-resistant cells in ESCC and may play a role in ESCC drug resistance.

摘要

目的

通过对食管鳞状细胞癌(ESCC)干细胞的分子特征分析,探讨ESCC干细胞在紫杉醇耐药中的作用。

方法

在人食管鳞状细胞癌系(EC109)中,采用间歇性诱导和高剂量紫杉醇时间递增的方法建立细胞耐药系(RR-ECl09)。通过MTT法评估RR-ECl09细胞对抗癌药物的多药耐药性。将RR-EC109和EC109细胞用于成球试验、克隆形成试验、干细胞基因表达以及上皮-间质转化标志物的表达检测。

结果

RR-EC109细胞系建立超过7个月。RR-ECl09细胞对紫杉醇具有67.258倍的耐药性。RR-EC109细胞的成球率和克隆增殖能力百分比高于EC109细胞(P<0.05)。RR-EC109细胞中侧群细胞数量高于EC109细胞(P<0.05)。RR-EC109细胞产生的Bmi1、Nanog、Oct4、Sox2、ABCG2、Nestin和Ki-67的mRNA比EC109细胞更多(P<0.05)。RR-EC109细胞中E-钙黏蛋白表达低于EC109细胞,而N-钙黏蛋白、Snail和Twist表达高于EC109细胞(P<0.05)。

结论

ESCC中紫杉醇耐药细胞中存在癌干细胞(CSC)样细胞,可能在ESCC耐药中发挥作用。

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