Abstract：
BACKGROUND: Nasopharyngeal carcinoma (NPC) is an aggressive and highly metastatic malignant tumor. Despite recent therapeutic advances, resistance to Taxol (the generic name of paclitaxel) therapy remains a major challenge in clinical management. Therefore, it is imperative to explore the potential mechanisms of paclitaxel resistance in NPC. This study aimed to investigate the expression of aldehyde dehydrogenase 2 (ALDH2) in NPC cells and its critical role in paclitaxel resistance.
METHODS: Paclitaxel-resistant cell line CNE1/Taxol (CNE1-TR), a drug-resistant cell line, was established by exposing the CNE1 nasopharyngeal carcinoma cell line to progressively increasing concentrations of paclitaxel. Furthermore, we investigated the role of ALDH2 in paclitaxel resistance and the function of exosomes using cell culture, Western blotting, reverse transcription-polymerase chain reaction (RT-PCR), Cell Counting Kit-8 (CCK-8), and nanoparticle tracking analysis.
RESULTS: The results showed that in the presence of paclitaxel, the CNE1-TR cells manifested higher survival rate and half-maximal inhibitory concentration (IC50) value compared to the parental cell line, indicating strong resistance to paclitaxel. CNE1-TR cells had significantly upregulated mRNA and protein levels of ALDH2. In addition, exosome analysis showed that CNE1-TR cells were able to deliver ALDH2 via exosomes, increasing paclitaxel resistance in the recipient cells. We observed that the ALDH2 expression levels and paclitaxel resistance in CNE1-TR cells were effectively reduced by blocking the release of exosomes.
CONCLUSIONS: ALDH2 is not only a key molecular marker indicative of therapeutic efficacy, but also a potential therapeutic target for developing novel anticancer strategies. By blocking the exosomal transport of ALDH2 or directly inhibiting its activity, it may be possible to overcome paclitaxel resistance, thus improving the success rate of clinical treatment.
METHODS: Paclitaxel-resistant cell line CNE1/Taxol (CNE1-TR), a drug-resistant cell line, was established by exposing the CNE1 nasopharyngeal carcinoma cell line to progressively increasing concentrations of paclitaxel. Furthermore, we investigated the role of ALDH2 in paclitaxel resistance and the function of exosomes using cell culture, Western blotting, reverse transcription-polymerase chain reaction (RT-PCR), Cell Counting Kit-8 (CCK-8), and nanoparticle tracking analysis.
RESULTS: The results showed that in the presence of paclitaxel, the CNE1-TR cells manifested higher survival rate and half-maximal inhibitory concentration (IC50) value compared to the parental cell line, indicating strong resistance to paclitaxel. CNE1-TR cells had significantly upregulated mRNA and protein levels of ALDH2. In addition, exosome analysis showed that CNE1-TR cells were able to deliver ALDH2 via exosomes, increasing paclitaxel resistance in the recipient cells. We observed that the ALDH2 expression levels and paclitaxel resistance in CNE1-TR cells were effectively reduced by blocking the release of exosomes.
CONCLUSIONS: ALDH2 is not only a key molecular marker indicative of therapeutic efficacy, but also a potential therapeutic target for developing novel anticancer strategies. By blocking the exosomal transport of ALDH2 or directly inhibiting its activity, it may be possible to overcome paclitaxel resistance, thus improving the success rate of clinical treatment.
摘要：
背景：鼻咽癌（NPC）是一种侵袭性高转移的恶性肿瘤。尽管最近的治疗进展，对紫杉醇(紫杉醇的通用名)治疗的耐药性仍然是临床管理中的主要挑战.因此,探讨鼻咽癌紫杉醇耐药的潜在机制势在必行。本研究旨在探讨醛脱氢酶2(ALDH2)在鼻咽癌细胞中的表达及其在紫杉醇耐药中的作用。
方法：紫杉醇耐药细胞株CNE1/Taxol(CNE1-TR),耐药细胞系,通过将CNE1鼻咽癌细胞系暴露于逐渐增加浓度的紫杉醇而建立。此外，我们使用细胞培养研究了ALDH2在紫杉醇耐药性中的作用和外泌体的功能，西方印迹,逆转录-聚合酶链反应(RT-PCR),细胞计数套件-8（CCK-8），和纳米粒子跟踪分析。
结果：结果表明，在紫杉醇的存在下，与亲本细胞系相比，CNE1-TR细胞表现出更高的存活率和半最大抑制浓度（IC50）值，表明对紫杉醇有较强的耐药性。CNE1-TR细胞具有显著上调的ALDH2的mRNA和蛋白水平。此外,外泌体分析显示CNE1-TR细胞能够通过外泌体递送ALDH2，增加受体细胞对紫杉醇的耐药性。我们观察到，通过阻断外泌体的释放，CNE1-TR细胞中的ALDH2表达水平和紫杉醇抗性有效降低。
结论：ALDH2不仅是指示治疗效果的关键分子标志物，也是开发新的抗癌策略的潜在治疗目标。通过阻断ALDH2的外泌体转运或直接抑制其活性，有可能克服紫杉醇耐药性，从而提高临床治疗的成功率。
方法：紫杉醇耐药细胞株CNE1/Taxol(CNE1-TR),耐药细胞系,通过将CNE1鼻咽癌细胞系暴露于逐渐增加浓度的紫杉醇而建立。此外，我们使用细胞培养研究了ALDH2在紫杉醇耐药性中的作用和外泌体的功能，西方印迹,逆转录-聚合酶链反应(RT-PCR),细胞计数套件-8（CCK-8），和纳米粒子跟踪分析。
结果：结果表明，在紫杉醇的存在下，与亲本细胞系相比，CNE1-TR细胞表现出更高的存活率和半最大抑制浓度（IC50）值，表明对紫杉醇有较强的耐药性。CNE1-TR细胞具有显著上调的ALDH2的mRNA和蛋白水平。此外,外泌体分析显示CNE1-TR细胞能够通过外泌体递送ALDH2，增加受体细胞对紫杉醇的耐药性。我们观察到，通过阻断外泌体的释放，CNE1-TR细胞中的ALDH2表达水平和紫杉醇抗性有效降低。
结论：ALDH2不仅是指示治疗效果的关键分子标志物，也是开发新的抗癌策略的潜在治疗目标。通过阻断ALDH2的外泌体转运或直接抑制其活性，有可能克服紫杉醇耐药性，从而提高临床治疗的成功率。
