Silencing of the ARK5 gene reverses the drug resistance of multidrug-resistant SGC7901/DDP gastric cancer cells

PeerJ

Xiaowei Liu¹  Dan Liu¹  Hongtao Wan¹  Yanglin Chen¹  Ren Tang¹  Bo Yi² 

[1] Jiangxi Provincial Key Laboratory of Basic Pharmacology, Nanchang University School of Pharmaceutical Science, Nanchang, China;Second Abdominal Surgery Department, Jiangxi Province Tumor Hospital, Nanchang, China;

关键词: AMPK-related protein kinase 5 (ARK5);    Gastric cancer cells;    Multidrug resistance;    Adriamycin;    Cisplatin;    5-fluorouracil;   

DOI  :  10.7717/peerj.9560

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown