Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Phosphatidylethanolamine binding protein 1 enhances sensitivity of gastric cancer cell to 5-fluorouracil via inhibition of cell proliferation, migration and invasion

Mengxin Lin^1-3, Xiaoyan Lin^1-3, Xiaobing Huang^1-3, Qing Liu^1-3, Riping Wu^1-3, Xinli Wang^1-3, Dongta Zhong^1-3

¹Department of Medical Oncology, Fujian Medical University Union Hospital; ²Fujian Key Laboratory of Translational Cancer Medicine; ³Fujian Medical University Stem Cell Research Institute, Fuzhou 350001, Fujian, PR China.

For correspondence:- Dongta Zhong Email: qvxib1@163.com

Accepted: 23 November 2020 Published: 30 December 2020

Citation: Lin M, Lin X, Huang X, Liu Q, Wu R, Wang X, et al. Phosphatidylethanolamine binding protein 1 enhances sensitivity of gastric cancer cell to 5-fluorouracil via inhibition of cell proliferation, migration and invasion. Trop J Pharm Res 2020; 19(12):2583-2590 doi: 10.4314/tjpr.v19i12.15

© 2020 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To determine the association between phosphatidylethanolamine binding protein 1, which is an Raf kinase inhibitor protein (RKIP), and 5-fluorouracil (5-FU) via analysis of the association between RKIP and clinical responses in individuals treated using fluorouracil-based chemotherapy.

Methods: Human gastric cancer cell lines MGC-803 and SGC-7901 were used in this study. Cell viability was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis and migration were determined with flow cytometry and Transwell chamber assays, respectively. The mRNA and protein expressions of apoptosis-related factors were assayed using real-time polymerase chain reaction (RT-PCR) and Western blotting, respectively, while the expression of RKIP was determined by immunohistochemical staining.

Results: Chemotherapeutic drug (5-FU) treatment induced low RKIP expression levels in tumorigenic GC cells, thereby sensitizing the cells to apoptosis (8.57 vs 1.25 %, p < 0.01). The highest RKIP level correlated well with initiation of apoptosis (4.20 vs 1.25 %, p < 0.01). Following in vitro downregulation of RKIP, there was increase in the viability and proliferation of RKIP-inhibited cells over time, and these changes were linked to alterations in cell cycle phases and increased optical density in MTT proliferation assay (1.55 vs 1.18, p < 0.01). In vitro Transwell assay measurement revealed an association between RKIP downregulation and enhancement of cell migration potential (652 vs 436, p < 0.01). Ectopic RKIP expression restored the apoptotic sensitivity of resistant cells (14.30 vs 1.36 %, p < 0.01). This sensitization was annulled by upregulation of survival routes. Reduction of RKIP by expression of antisense and siRNA conferred resistance on cancer cells sensitive to 5-FU-mediated apoptosis (6.88 vs 2.13 %, p < 0.01).

Conclusion: Thus, RKIP is a promising therapeutic strategy for improving the efficacy of clinically relevant chemotherapeutic drugs for GC.

Keywords: Gastric cancer, Raf kinase inhibitor protein, Cell proliferation, Invasion, Apoptosis, Chemotherapy, Phosphatidylethanolamine binding protein 1