RETRACTED: Effect of PLK1 inhibition on cisplatin‐resistant gastric cancer cells

Abstract

Objective: This study aims to investigate the effect of polo-like kinase 1 (PLK1) inhibition on cisplatin (DDP)-resistant gastric cancer (GC) cells. Methods: The transcriptional level of PLK1 was measured by quantitative reverse-transcription polymerase chain reaction. Expressions of PLK1 and its downstream mediators as well as autophagy-related protein LC3 I/LC3 II were detected by western blot. An 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and 5-ethynyl-2′deoxyuridine immunofluorescent staining were conducted to evaluate the cell viability and replication activity separately. Flow cytometry was carried out to determine the cell cycle status. The GFP-LC3 vector contributed toward tracking the formation and aggregation of autophagosomes. Results: Drug-resistant SGC-7901/DDP cells showed insignificant changes in all phases after DDP treatment, including DNA replication, cell proliferation, cell cycle, and apoptosis, whereas DDP could significantly improve the autophagy level of SGC-7901/DDP as well as PLK1 expression. By downregulating the expression of PLK1, both BI2536 and si-PLK1 enhanced SGC-7901/DDP sensitivity to DDP, suppressing the proliferation and autophagy as well as improving the apoptosis rate. PLK1 inhibition also resulted in the repression of cell division regulators CDC25C and cyclin B1. Conclusion: Together, our experimental results illustrated that the DDP resistance of GC cells might be associated with the aberrant overexpression of PLK1. PLK1 inhibition, including si-PLK1 and BI2536 treatment, could restore the chemosensitivity of drug-resistant SGC-7901/DDP cells and enhance the efficacy of DDP, revealing the potential value of PLK1 inhibition in GC chemotherapy. K E Y W O R D S autophagy, BI2536, cisplatin, gastric cancer, PLK1

High FAM189B Expression and Its Prognostic Value in Patients with Gastric Cancer

“…In this study, we also showed the clinical significance of two hub genes (CHEK2 and PLK1) in the cell cycle pathway and their correlations with FAM189B. Both of these two coexpressed genes of FAM189B have been well reported to play essential roles in the cell cycle regulation and development of GC [30][31][32][33][34]. Although there was only preliminary evidence of a correlation, this finding also suggests that FAM189B may affect the clinical progression of GC by disturbing the cell cycle of GC cells.…”

<p>MiR-1224-5p Activates Autophagy, Cell Invasion and Inhibits Epithelial-to-Mesenchymal Transition in Osteosarcoma Cells by Directly Targeting PLK1 Through PI3K/AKT/mTOR Signaling Pathway</p>

“…33 It has been reported that overexpression of PLK1 can promote the progression of breast cancer, 33 renal cell carcinoma, 34 gastric cancer. 35 With regard to the study of PLK1 in OS, Zhu et al found that the proliferation of OS cells was inhibited with the intervention of PLK1 expression. 36 Mo et al found that PLK1 could promote the proliferation of MYC-amplifying OS cells through autophagy.…”

The Role of Autophagy in Gastric Cancer Chemoresistance: Friend or Foe?

“…It has been found that WASF3 overexpression induces autophagy by increasing ATG12 level and causes OXA resistance in gastric cancer cells, while interference with WASF3 can reverse OXA resistance in vitro (Nie et al, 2020). Chen et al (2019) have demonstrated that the expression of polo-like kinase 1 (PLK1) is significantly increased in cisplatin (DDP)-resistant SGC-7901/DDP cells, whereas PLK1 knockdown inhibits autophagy, increases apoptosis, and restores the chemosensitivity of DDPresistant cells. Aquaporins (AQPs) are a family of small integral membrane proteins; among them, AQP3 is highly expressed in gastric cancer tissues (Moosavi and Elham, 2020).…”