芦文萱,唐伏秋,吴子熹,等.WP1130通过下调β-catenin增强鼻咽癌细胞化疗敏感性[J].肿瘤学杂志,2022,28(8):664-671. |
WP1130通过下调β-catenin增强鼻咽癌细胞化疗敏感性 |
WP1130 Enhances Chemosensitivity by Downregulating β-catenin Expression in Nasopharyngeal Carcinoma Cells |
投稿时间:2021-12-06 |
DOI:10.11735/j.issn.1671-170X.2022.08.B007 |
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中文关键词: 鼻咽癌 顺铂 WP1130 β-catenin 增殖 迁移 侵袭 |
英文关键词:nasopharyngeal carcinoma cisplatin WP1130 β-catenin proliferation migration invasion |
基金项目:湖北省卫生健康委科研项目(WJ2021M221);武汉中青年医学骨干人才培养工程 |
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中文摘要: |
摘 要:[目的]探讨WP1130与顺铂联合用药对鼻咽癌细胞增殖和转移的影响及其可能机制。[方法] CCK-8法检测鼻咽癌顺铂敏感细胞系HNE1和顺铂耐药细胞系HNE1/DDP的顺铂药物半抑制浓度(IC50),以及不同浓度WP1130对鼻咽癌细胞活力的影响;选取适当药物浓度处理细胞,两种鼻咽癌细胞系分别分为4组:空白对照组(DMSO)、DDP单药组(6 ?滋mol/L顺铂)、WP1130单药组(1.25 ?滋mol/L WP1130)以及DDP+WP1130联合用药组(6 ?滋mol/L顺铂+1.25 ?滋mol/L WP1130)。MTT法检测鼻咽癌细胞增殖能力;细胞划痕实验检测鼻咽癌细胞迁移能力;Transwell侵袭实验检测鼻咽癌细胞侵袭能力;RT-PCR和Western blot实验检测顺铂耐药HNE1/DDP与亲本HNE1鼻咽癌细胞中β-catenin的表达情况以及不同药物处理对β-catenin的表达的影响。[结果] 耐药HNE1/DDP细胞比亲本HNE1细胞对顺铂的耐受性提高了近5.7倍(5.17±0.33 vs 29.44±2.62,P<0.01)。β-catenin在HNE1/DDP细胞中的mRNA表达上调约3.4倍(1.00±0.26 vs 3.44±0.39,P<0.01)。与空白对照组和单药组相比,顺铂+WP1130联合用药组细胞中β-catenin的表达显著下调(HNE1:1.00±0.06 vs 0.78±0.07 vs 0.32±0.05,P<0.05;HNE1/DDP:1.01±0.05 vs 0.57±0.07 vs 0.39±0.07,P<0.05),顺铂+WP1130联合用药组细胞增殖、迁移和侵袭能力均显著下降(P均<0.01)。[结论] WP1130与顺铂联合用药可以通过下调β-catenin的表达增强顺铂对细胞增殖、迁移和侵袭的抑制作用,从而增强鼻咽癌细胞的化疗敏感性。 |
英文摘要: |
Abstract:[Objective] To explore effect of WP1130 combined with cisplatin on proliferation and metastasis of nasopharyngeal carcinoma(NPC) cells and its possible mechanism. [Methods] The IC50 of human NPC HNE1 cells(sensitive to cisplatin) and HNE1/DDP cells(resistant to cisplatin) to cisplatin was detected with CCK-8 assay. The HNE1 and HNE1/DDP cells were treated with no drugs(control group), 6 mol/L cisplatin(DDP group), 1.25 mol/L WP1130(WP1130 group), or 6 mol/L cisplatin plus 1.25 mol/L WP1130(DDP+WP1130 group), respectively. The cell proliferation was detected with MTT assay; cell migration ability was detected with wound-healing assay; cell invasion ability was detected with Transwell invasion assay; the expression of β-catenin mRNA and protein was detected with RT-PCR and Western blot, respectively. [Results] The IC50 of HNE1/DDP cells to cisplatin was 5.7 fold(5.17±0.33 vs 29.44±2.62, P<0.01) higher than that of HNE1 cells. The mRNA expression of β-catenin in HNE1/DDP cells was increased by 3.4 fold(1.00±0.26 vs 3.44±0.39, P<0.01). Compared with the blank control group and single drug group, the expression of β-catenin decreased significantly in cisplatin +WP1130 group(HNE1: 1.00±0.06 vs 0.78±0.07 vs 0.32±0.05, P<0.05; HNE1/DDP:1.01±0.05 vs 0.57±0.07 vs 0.39±0.07, P<0.05), the proliferation, migration and invasion ability of cells in cisplatin+WP1130 group were significantly decreased(all P<0.01). [Conclusion] WP1130 can enhance the inhibiting effect of cisplatin in cell proliferation, migration and invasion in drug-resistant NPC cells and this chemosensitivity-enhancing effect is associated with the down-regulating β-catenin expression in NPC cells. |
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