Silencing of the ARK5 gene reverses the drug resistance of multidrug-resistant SGC7901/DDP gastric cancer cells
Silencing of the ARK5 gene reverses the drug resistance of multidrug-resistant SGC7901/DDP gastric cancer cells
复制标题
DOI：
10.7717/peerj.9560
复制
发表时间：
2020-08
期刊：
影响因子：
2.7
通讯作者：
Hong-ping Wan;Xiaowei Liu;Yanglin Chen;Ren Tang;B. Yi;Dan Liu
中科院分区：
文献类型：
--
作者：
Hong-ping Wan;Xiaowei Liu;Yanglin Chen;Ren Tang;B. Yi;Dan Liu
多年来，胃癌细胞的多药耐药（MDR）一直是世界范围内化疗过程中的一个棘手问题，亟待解决。本文报道了ARK5基因在体外和体内均可促进胃癌细胞的多药耐药。本研究利用LV-ARK5-RNAi慢病毒转染亲本细胞系SGC7901和MDR细胞系SGC7901/DDP，构建稳定的ARK5干扰模型。随后，用顺铂（DDP）、阿霉素（ADR）、5-氟尿嘧啶（5-FU）和多西紫杉醇（DR） 4种化疗药物处理细胞，并进行CCK8、菌落形成、阿霉素积累和保留、细胞凋亡等检测。研究发现，在体外，ARK5在MDR胃癌细胞中的表达明显高于亲本细胞。此外，在不同化疗药物的作用下，与亲本细胞相比，MDR细胞也具有更高的细胞存活率、更高的集落形成数、更高的药物泵送率和更低的细胞凋亡率。此外，在异种移植小鼠模型中，ARK5高表达的MDR细胞对化疗药物的耐药性高于亲本细胞。综上所述，本研究揭示沉默ARK5基因可有效逆转MDR胃癌细胞对化疗药物的耐药，揭示其抑制MDR细胞主动泵出能力的机制。
For several years, the multidrug resistance (MDR) of gastric cancer cells has been a thorny issue worldwide regarding the chemotherapy process and needs to be solved. Here, we report that the ARK5 gene could promote the multidrug resistance of gastric cancer cells in vitro and in vivo. In this study, LV-ARK5-RNAi lentivirus was used to transfect the parental cell line SGC7901 and MDR cell line SGC7901/DDP to construct a stable model of ARK5 interference. Subsequently, the cells were treated with four chemotherapeutic drugs, cisplatin (DDP), adriamycin (ADR), 5-fluorouracil (5-FU) and docetaxel (DR) and were subjected to the CCK8, colony formation, adriamycin accumulation and retention, cell apoptosis and other assays. The study found that, in vitro, the expression of ARK5 in MDR gastric cancer cells was significantly higher than that in parental cells. Additionally, when treated with different chemotherapeutic drugs, compared with parental cells, MDR cells also had a higher cell survival rate, higher colony formation number, higher drug pump rate, and lower cell apoptosis rate. Additionally, in xenograft mouse models, MDR cells with high ARK5 expression showed higher resistance to chemotherapeutic drugs than parental cells. Overall, this study revealed that silencing the ARK5 gene can effectively reverse the drug resistance of MDR gastric cancer cells to chemotherapeutic drugs, providing insights into the mechanism of this process related to its inhibition of the active pump-out ability of MDR cells.