Role and mechanism of Twist1 in modulating the chemosensitivity of FaDu cells.
Role and mechanism of Twist1 in modulating the chemosensitivity of FaDu cells.
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Twist1 在调节 FaDu 细胞化学敏感性中的作用和机制
DOI：
10.3892/mmr.2014.2212
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发表时间：
2014-07
影响因子：
3.4
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Lu S;Yu L;Mu Y;Ma J;Tian J;Xu W;Wang H
多药耐药（MDR）是影响多种类型癌症化疗疗效的最重要障碍之一。在本研究中，我们证实了Twist 1在头颈部鳞状细胞癌（HNSCC）化疗敏感性中的可能作用，并确定其机制可能与MDR 1/P-gp调节有关。为了研究这一点，下咽癌细胞系FaDu，和它的多药耐药细胞系Taxol诱导，FaDu/T，使用。还进行了基于FaDu的靶向Twist 1过表达和Twist 1沉默的稳定转染子。通过形态学观察、流式细胞术、逆转录-聚合酶链反应（RT-PCR）、蛋白质印迹和激光扫描共聚焦显微镜检测Twist 1与FaDu细胞化疗敏感性的关系。我们的结果表明，Twist 1和MDR 1/P-gp在FaDu/T细胞中以MDR剂量依赖性方式上调。在MDR进展过程中，FaDu/T细胞的抗凋亡能力增强，凋亡相关蛋白（Bcl-2、Bax、活化的caspase-3和caspase-9）发生变化以抵抗凋亡。Twist 1过表达可降低细胞对紫杉醇的敏感性，MDR 1/P-gp和IC 50显著增加（P<0.05）。这种过表达还增强了细胞对凋亡的抵抗，凋亡蛋白改变以抵抗细胞死亡，并抑制紫杉醇诱导的Ca 2+释放（P<0.05）。Twist 1沉默细胞中的检测也证实了这一结果。该研究提供了证据表明Twist 1表达的改变调节FaDu细胞对紫杉醇的化学敏感性。因此，Twist 1基因敲减可能是治疗晚期下咽癌MDR的一种有前景的治疗方案。
Multidrug resistance (MDR) is one of the most important obstacles affecting the efficacy of chemotherapy treatments for numerous types of cancer. In the present study, we have demonstrated the possible function of Twist1 in the chemosensitivity of head and neck squamous cell carcinoma (HNSCC) and have identified that its mechanism maybe associated with MDR1/P-gp regulation. To investigate this, the hypopharyngeal cancer cell line, FaDu, and its MDR cell line induced by taxol, FaDu/T, were employed. Stable transfectants targeted to Twist1 overexpression and Twist1 silencing based on FaDu were also conducted. Morphological observation, flow cytometry, reverse transcription-polymerase chain reaction (RT-PCR), western blotting and laser scanning confocal microscope detection were utilized to detect the associations between Twist1 and the chemosensitivity of FaDu cells. Our results demonstrated that Twist1 and MDR1/P-gp were upregulated in FaDu/T cells in a MDR dose-dependent manner. The anti-apoptotic capabilities of FaDu/T cells were enhanced during MDR progression, with apoptosis-related proteins (Bcl-2, Bax, activated caspase-3 and caspase-9) changing to resist apoptosis. Twist1 overexpression decreased the sensitivity of cells to taxol as revealed by a significant increase in MDR1/P-gp and IC50 (P<0.05). This overexpression also enhanced the resistance to apoptosis, with apoptotic proteins changing to resist cell death, and inhibited Ca2+ release induced by taxol (P<0.05). Detections in Twist1 silencing cells also confirmed this result. This study provided evidence that alterations of Twist1 expression modulates the chemosensitivity of FaDu cells to taxol. Therefore, Twist1 knockdown may be a promising treatment regimen for advanced hypopharyngeal carcinoma patients with MDR.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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影响因子：
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作者：
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DOI：
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发表时间：
2011-03-01
期刊：
Cancer imaging : the official publication of the International Cancer Imaging Society
影响因子：
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作者：
Dizdarevic S;Peters AM
通讯作者：
Peters AM
影响因子：
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作者：
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