CD133/ABCC5 宫颈癌细胞具有癌症干细胞特性。

CD133/ABCC5 cervical cancer cells exhibit cancer stem cell properties.

作者信息

He Lin, Qian Hengjun, Seyiti Ayinuer, Yang Chengshaoxiong, Shi Ning, Chen Chen, Zhang Pingxu, Hou Youxiang

机构信息

Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi, Xinjiang, 830011, PR China.

Yibin Second People's Hospital, Sichuan, 644002, PR China.

出版信息

Heliyon. 2024 Aug 29;10(17):e37066. doi: 10.1016/j.heliyon.2024.e37066. eCollection 2024 Sep 15.

DOI:10.1016/j.heliyon.2024.e37066

PMID:39296204

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11408061/

Abstract

OBJECTIVE

This study explores the correlation between Forkhead box M1 (FOXM1) and ATP-binding cassette subfamily C member 5 (ABCC5) in relation to paclitaxel resistance in cervical cancer. It aims to identify potential cervical cancer stem cell markers, offering fresh perspectives for developing therapeutic strategies to overcome paclitaxel chemoresistance in cervical cancer.

METHODS

Paclitaxel-resistant Hela cells (Hela/Taxol) were developed by intermittently exposing Hela cells to progressively increasing concentrations of paclitaxel. We assessed the biological properties of both Hela and Hela/Taxol cells using various assays: cell proliferation, clonogenic, cell cycle, apoptosis, scratch, and transwell. To determine which markers better represent tumor stem cells, we analyzed various known and potential stem cell markers in combination. Flow cytometry was employed to measure the proportion of positive markers in both parental and drug-resistant cell lines. Following statistical analysis to establish relative stability, CD133+ABCC5+ cells were sorted for further examination. Subsequent tests included sphere-forming assays and Western blot analysis to detect the presence of the stem cell-specific protein Sox2, aiding in the identification of viable cervical cancer stem cell markers.

RESULTS

The Hela/Taxol cell line exhibited significantly enhanced proliferation, migration, and invasion capabilities compared to the Hela cell line, alongside a marked reduction in apoptosis rates (P < 0.01). Notably, proportions of CD44, CD24CD44, ABCC5+, CD24CD44+ABCC5+, CD44+ABCC5+, CD24CD44+FOXM1+, CD44+FOXM1+, CD133+ABCC5+, and CD133+FOXM1+ were significantly higher (P < 0.05). Furthermore, the size and number of spheres formed byCD133+ABCC5+ cells were greater in the sorted Hela/Taxol line (P < 0.01), with increased expression of the stem cell marker Sox2 (P < 0.001).

CONCLUSION

The Hela/Taxol cells demonstrate increased tumoral stemness, suggesting that CD133+ABCC5+ may serve as a novel marker for cervical cancer stem cells.

摘要

目的

本研究探讨叉头框蛋白M1（FOXM1）与ATP结合盒转运体C亚家族成员5（ABCC5）之间的相关性及其与宫颈癌紫杉醇耐药性的关系。旨在识别潜在的宫颈癌干细胞标志物，为制定克服宫颈癌紫杉醇化疗耐药性的治疗策略提供新的视角。

方法

通过将Hela细胞间歇性暴露于逐渐增加浓度的紫杉醇中，建立紫杉醇耐药的Hela细胞系（Hela/Taxol）。我们使用多种检测方法评估Hela和Hela/Taxol细胞的生物学特性：细胞增殖、克隆形成、细胞周期、凋亡、划痕和Transwell实验。为了确定哪些标志物能更好地代表肿瘤干细胞，我们综合分析了各种已知和潜在的干细胞标志物。采用流式细胞术测量亲本细胞系和耐药细胞系中阳性标志物的比例。经过统计分析以确定相对稳定性后，对CD133+ABCC5+细胞进行分选以进一步检测。后续实验包括成球实验和蛋白质免疫印迹分析，以检测干细胞特异性蛋白Sox2的表达情况，辅助鉴定可行的宫颈癌干细胞标志物。

结果

与Hela细胞系相比，Hela/Taxol细胞系表现出显著增强的增殖、迁移和侵袭能力，同时凋亡率显著降低（P<0.01）。值得注意的是，CD44、CD24CD44、ABCC5+、CD24CD44+ABCC5+、CD44+ABCC5+、CD24CD44+FOXM1+、CD44+FOXM1+、CD133+ABCC5+和CD133+FOXM1+的比例显著更高（P<0.05）。此外，在分选的Hela/Taxol细胞系中，CD133+ABCC5+细胞形成的球体大小和数量更大（P<0.01），干细胞标志物Sox2的表达增加（P<0.001）。