谷胱甘肽 S-转移酶-在肺癌干细胞顺铂耐药中的潜在作用。
Potential Role of GST- in Lung Cancer Stem Cell Cisplatin Resistance.
机构信息
Department of Respiratory Diseases, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China.
Department of Respiratory Diseases, Ganzhou Affiliated Hospital of Nanchang University, Ganzhou, Jiangxi 341000, China.
出版信息
Biomed Res Int. 2021 Nov 19;2021:9142364. doi: 10.1155/2021/9142364. eCollection 2021.
BACKGROUND
Cancer stem cells (CSCs) are responsible for tumorigenesis, chemoresistance, and metastasis. Chemoresistance is a major challenge in the management of lung cancer. Glutathione-sulphur-transferase- (GST-) plays an important role in the origin and development of various types of cancer by regulating the cellular redox balance. Recent investigations have demonstrated that GST- is associated with the chemoresistance of lung CSCs (LCSCs). However, the mechanism of GST- in lung cancer, particularly in LCSCs, remains unclear. The present study is aimed at exploring the potential role of GST- in stemness and cisplatin (DDP) resistance of LCSCs. . In the present study, lung cancer cell spheres were established using the A549 cell line, which according to our previous research, was confirmed to exhibit characteristics of stem cells. Next, GST- protein expression, apoptosis percentage, and intracellular reactive oxygen species (ROS) concentration in A549 adherent cells and A549 cell spheres were analyzed by western blotting and flow cytometry, respectively. Finally, DDP resistance, ROS concentration, and GST- expression in LCSCs were analyzed following the interference with GST- using DL-buthionine-(S,R)-sulphoximine and N-acetylcysteine.
RESULTS
The results revealed that GST- was highly expressed in A549 cell spheres compared with A549 adherent cells and was associated with a decreased intracellular ROS concentration (both < 0.05). Regulating GST- protein expression could alter DDP resistance of LCSCs by influencing ROS.
CONCLUSION
These results suggested that GST- may be important for LCSC drug resistance by downregulating ROS levels. These findings may contribute to the development of new adjuvant therapeutic strategies for lung cancer.
背景
癌症干细胞（CSCs）是肿瘤发生、化疗耐药和转移的原因。化疗耐药是肺癌治疗的主要挑战。谷胱甘肽硫转移酶（GST）通过调节细胞内氧化还原平衡，在各种类型癌症的发生和发展中发挥重要作用。最近的研究表明，GST与肺癌 CSCs（LCSCs）的化疗耐药有关。然而，GST在肺癌中的作用机制，特别是在 LCSCs 中，尚不清楚。本研究旨在探讨 GST 在 LCSCs 干性和顺铂（DDP）耐药中的潜在作用。在本研究中，使用 A549 细胞系建立了肺癌肿瘤球，根据我们之前的研究，该细胞系被证实具有干细胞特征。接下来，通过 Western blot 和流式细胞术分别分析 A549 贴壁细胞和 A549 肿瘤球中的 GST-蛋白表达、细胞凋亡率和细胞内活性氧（ROS）浓度。最后，用 DL-丁硫氨酸-（S，R）-亚砜和 N-乙酰半胱氨酸干扰 GST-后，分析 LCSCs 的 DDP 耐药性、ROS 浓度和 GST-表达。结果：结果表明，与 A549 贴壁细胞相比，GST-在 A549 肿瘤球中高度表达，并且与细胞内 ROS 浓度降低有关（均<0.05）。调节 GST-蛋白表达可以通过影响 ROS 来改变 LCSCs 的 DDP 耐药性。结论：这些结果表明，GST-可能通过下调 ROS 水平对 LCSC 耐药性很重要。这些发现可能有助于为肺癌开发新的辅助治疗策略。
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