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CD44+头颈部鳞状细胞癌细胞对凋亡诱导刺激的抵抗。

Resistance to apoptosis-inducing stimuli in CD44+ head and neck squamous cell carcinoma cells.

机构信息

Department of Otolaryngology-Head and Neck Surgery, University of Yamanashi, Faculty of Medicine, Chuo, Yamanashi, 409-3898, Japan.

出版信息

Head Neck. 2012 Mar;34(3):336-43. doi: 10.1002/hed.21732. Epub 2011 Apr 5.

Abstract

BACKGROUND

CD44 was identified previously as a surface marker in cancer stem cells (CSCs) of head and neck squamous cell carcinoma (HNSCC). Most cancer treatments have been linked to the activation of the apoptosis-signaling pathway; however, the resistance mechanisms to apoptosis in CSCs have not yet been fully elucidated.

METHODS

The sensitivity of CD44+ cells to diverse apoptosis-inducing stimuli was compared with that of CD44- cells. Furthermore, cell cycle changes and the expression of anti-apoptosis-related genes were examined using flow cytometry and real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR).

RESULTS

CD44+ cells were resistant to various apoptosis-inducing stimuli. Moreover, CD44+ cells showed a higher proportion of cells in G2/M phase of the cell cycle and upregulation of Bcl-2 and inhibitor of apoptosis (IAP) family genes compared with CD44- cells.

CONCLUSION

Treatment resistance in CSCs seems to be regulated by various mechanisms, and, therefore, additional treatment strategies to target CSCs are required in patients with HNSCC.

摘要

背景

CD44 先前被鉴定为头颈部鳞状细胞癌(HNSCC)癌症干细胞(CSC)的表面标志物。大多数癌症治疗都与凋亡信号通路的激活有关;然而,CSC 中对细胞凋亡的抵抗机制尚未完全阐明。

方法

比较了 CD44+细胞与 CD44-细胞对不同凋亡诱导刺激的敏感性。此外,使用流式细胞术和实时定量逆转录聚合酶链反应(RT-PCR)检查细胞周期变化和抗凋亡相关基因的表达。

结果

CD44+细胞对各种凋亡诱导刺激具有抗性。此外,与 CD44-细胞相比,CD44+细胞的细胞周期 G2/M 期比例更高,Bcl-2 和凋亡抑制因子(IAP)家族基因的表达上调。

结论

CSC 中的治疗耐药似乎受到多种机制的调节,因此需要针对 HNSCC 患者的 CSC 进行额外的治疗策略。

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