Flotillin-1 promotes progression and dampens chemosensitivity to cisplatin in gastric cancer via ERK and AKT signaling pathways

  • Eur J Pharmacol. 2022 Feb 5;916:174631. doi: 10.1016/j.ejphar.2021.174631.
Jiahui Wei  1 ,  Ruiqing Wang  2 ,  Yiran Lu  1 ,  Song He  1 ,  Yu Ding  3
Affiliations
  • 1. Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun, Jilin, 130062, PR China.
  • 2. The Eye Center in the Second Hospital of Jilin University, Ziqiang Street 218#, Nanguan District, Changchun City, Jilin, 130041, China.
  • 3. Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun, Jilin, 130062, PR China. Electronic address: [email protected].
PMID: 34774850 DOI: 10.1016/j.ejphar.2021.174631
Abstract

Background: Several past studies have reported the overexpression of Flotillin-1 in a variety of Cancer types. Cisplatin is a chemotherapeutic drug commonly used for Cancer treatment. The present study investigated the role of Flotillin-1 in the progression of GC and assessed whether it assists in the chemical sensitization of GC cells toward cisplatin.

Method: The expression of Flotillin-1 was detected both in human gastric mucosal cells and GC cells. Next, siRNA and shRNA were used to construct a stable cell line expressing low levels of Flotillin-1. Furthermore, the Cell Counting Kit 8 (CCK-8), flow cytometry, and transwell assays were employed to detect the impact of Flotillin-1 on GC cells. In addition, a nude mouse model of human GC was used to verify the knockdown of Flotillin-1 to increase the sensitivity of GC cells to cisplatin.

Results: Flotillin-1 was overexpressed in GC cells when compared to that in human gastric mucosal cells. The results for in vitro and vivo assays revealed that the knockdown of Flotillin-1 could significantly inhibit the proliferation of GC cells and increased the sensitivity of GC cells to cisplatin via the regulation of the protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) signaling pathway.

Conclusion: Flotillin-1 might be used as a molecular marker for GC diagnosis and could be explored as a potential new target for the treatment of GC.

Keywords
Chemosensitivity; Cisplatin; Flotillin-1; GC.
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