Tetramethylpyrazine-mediated regulation of CXCR4 in retinoblastoma is sensitive to cell density.
Tetramethylpyrazine-mediated regulation of CXCR4 in retinoblastoma is sensitive to cell density.
复制标题
四甲基吡嗪介导的视网膜母细胞瘤中 CXCR4 的调节对细胞密度敏感
DOI：
10.3892/mmr.2017.6293
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发表时间：
2017-05
影响因子：
3.4
通讯作者：
Zhuang J
中科院分区：
文献类型：
--
作者：
Wu N;Xu L;Yang Y;Yu N;Zhang Z;Chen P;Zhang J;Tang M;Yuan M;Ge J;Yu K;Zhuang J
视网膜母细胞瘤是儿童最常见的眼部肿瘤，它造成广泛的损害。目前视网膜母细胞瘤的治疗选择包括手术、化疗、放疗和冷冻疗法。然而，大多数化疗药物会引起并发症和副作用，导致患者健康严重受损。以往的研究报道，川芎嗪（TMP），这是一个提取物的中草药甘草，降低风险的多药耐药化疗和抑制增殖和转移的各种类型的癌细胞。然而，TMP在视网膜母细胞瘤中的潜在分子机制仍不清楚。目前的研究表明，C-X-C趋化因子受体4型（CXCR 4）在WERI-Rb 1细胞和视网膜母细胞瘤中表达。使用逆转录-定量聚合酶链反应和蛋白质印迹技术，目前的研究表明，TMP显着下调CXCR 4在高密度培养的WERI-Rb 1细胞的表达，而它在低密度WERI-Rb 1细胞有轻微的影响;此外，这种影响发生在一个时间依赖性的方式。TMP抑制WERI-Rb 1细胞增殖的效果与CXCR 4拮抗剂AMD 3100相当，这与CXCR 4在癌症发展中的作用一致。TMP对低密度（1×105 cells/ml）培养的细胞周期无明显影响，但对高密度（7.5×105 cells/ml）培养的细胞周期有明显影响（P<0.05）。此外，TMP处理显著下调原代大鼠视网膜神经细胞中CXCR 4的表达，并且这种处理保护原代大鼠视网膜神经细胞免受H2 O2诱导的损伤。因此，本研究的结果表明，TMP是用于治疗视网膜母细胞瘤的潜在候选者，并且还为该提取物的抗癌和神经保护作用的机制提供了新的见解。
Retinoblastoma is the most common ocular tumor in children, and it causes extensive damage. Current treatment options for retinoblastoma include surgery, chemotherapy, radiotherapy and cryotherapy. However, the majority of chemotherapy medicines cause complications and side effects that lead to severe impairment of patient health. Previous studies have reported that tetramethylpyrazine (TMP), which is an extract of the Chinese herbal medicine Chuanxiong, reduces the risk of multidrug resistance in chemotherapy and inhibits the proliferation and metastasis of various types of cancer cells. However, the underlying molecular mechanism of TMP in retinoblastoma remains unclear. The current study demonstrated that C-X-C chemokine receptor type 4 (CXCR4) was expressed in WERI-Rb1 cells and in retinoblastoma. Using reverse transcription-quantitative polymerase chain reaction and western blotting techniques, the current study demonstrated that TMP significantly downregulated the expression of CXCR4 in WERI-Rb1 cells cultured at high density, whereas it had a minor effect in low-density WERI-Rb1 cells; additionally, this effect occurred in a time-dependent manner. TMP inhibited the proliferation of WERI-Rb1 cells as effectively as a CXCR4 antagonist, AMD3100, consistent with a role of CXCR4 in cancer development. Notably, TMP did not affect the cell cycle of cells cultured at low density (1×105 cells/ml), whereas it induced G1-phase arrest in high-density cells (7.5×105 cells/ml; P<0.05). In addition, the expression of CXCR4 in primary rat retinal neurocytes was significantly downregulated by TMP treatment, and this treatment protected primary rat retinal neurocytes from H2O2-induced damage. Thus, the results of this study indicate that TMP is a potential candidate for use in treatment of retinoblastoma, and also provides novel insights into the mechanisms of the anti-cancer and neuroprotective effects of this extract.