摘要
目的: 本研究旨在分析胱硫醚β合酶(CBS)是否在肝细胞癌(HCC)耐药中起作用。 方法: 采用MTS法检测化疗药物阿霉素(DOX)和舒尼替尼对肝癌细胞存活和生长的影响。通过细胞内阿霉素积累试验,评价阿霉素和舒尼替尼对肝癌细胞的敏感性及多药耐药相关蛋白P-糖蛋白(P-gp)的作用。采用亚甲蓝法对硫化氢产量进行了定量分析。细胞内活性氧的产生用DCFHDA分析定量。采用刮伤法和穿孔法测定细胞迁移和侵袭情况。蛋白质的表达通过蛋白质印迹分析检测。 结果: 高CBS表达的HepG2细胞对DOX和sunitinib的敏感性较低,CBS的敲除显著提高了HepG2细胞对DOX和sunitinib的敏感性。相比之下,CBS过度表达增加了BEL-7404细胞对DOX和舒尼替尼的抵抗力。此外,CBS的过度表达导致了BEL-7404细胞P-gp表达水平的上调和DOX积累的减少。在进一步的机制研究中,我们发现Stat3/Akt/Bcl-2通路的激活、活性氧抑制以及提高肝癌细胞的转移能力是肝细胞癌耐药的主要原因。 结论: CBS过度表达导致肝癌细胞抵抗.
关键词: 胱硫醚β合酶,多药耐药,转移,肝癌,DOX,GST。
Current Molecular Medicine
Title:Cystathionine β-synthase Induces Multidrug Resistance and Metastasis in Hepatocellular Carcinoma
Volume: 18 Issue: 7
关键词: 胱硫醚β合酶,多药耐药,转移,肝癌,DOX,GST。
摘要: Objective: This study aims to analyze whether Cystathionine β-synthase (CBS) plays roles in hepatocellular carcinoma (HCC) drug resistance.
Methods: MTS assay was used to detect the effect of chemotherapeutic drugs doxorubicin (DOX) and sunitinib on HCC cell viability and cell growth. Intracellular doxorubicin accumulation assay was performed to evaluate the sensitivity of DOX and sunitinib in HCC cells and the function of multidrug resistance-associated protein Pglycoprotein (P-gp). Quantification of H2S production was performed using the methylene blue method. Production of intracellular ROS was quantified using the DCFHDA assay. The scratch wound and transwell assays were used to determine the cell migration and invasion. Expression of proteins was tested by western blot analysis.
Results: HepG2 cells with high CBS expression were less sensitive to DOX and sunitinib and knockdown of CBS significantly elevated the sensitivity to DOX and sunitinib in HepG2 cells. In contrast, CBS overexpression increased the resistance of DOX and sunitinib in BEL-7404 cells. Moreover, the overexpression of CBS caused the up-regulation of the expression level of P-gp and the decrease of DOX accumulation in BEL-7404 cells. In further mechanism research, we found that STAT3/Akt/Bcl-2 pathway activation, reactive oxygen species (ROS) inhibition as well as enhancement of the metastatic ability of hepatoma cells were responsible for the HCC drug resistance.
Conclusion: CBS overexpression conferred HCC cell resistance.
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Cite this article as:
Cystathionine β-synthase Induces Multidrug Resistance and Metastasis in Hepatocellular Carcinoma, Current Molecular Medicine 2018; 18 (7) . https://dx.doi.org/10.2174/1566524019666181211162754
DOI https://dx.doi.org/10.2174/1566524019666181211162754 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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