Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Inhibition of gastric cancer cell growth, invasion and metastasis by tocotrienolic amide

Yi Huang, Shi Xu

Department of General Surgery, The People's Hospital of Suzhou New District, Suzhou, Jiangsu 215129, China;

For correspondence:- Shi Xu Email: WShiXu12@yahoo.com Tel:+8613277611231

Accepted: 20 November 2020 Published: 31 December 2020

Citation: Huang Y, Xu S. Inhibition of gastric cancer cell growth, invasion and metastasis by tocotrienolic amide. Trop J Pharm Res 2020; 19(12):2603-2608 doi: 10.4314/tjpr.v19i12.18

© 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 investigate the effect of tocotrienolic amide on gastric cancer (GC) cell growth and metastasis, and the underlying mechanism of action.

Methods: Gastric cancer (GC) cell lines MKN28 and NCI-N87 were cultured in Dulbecco's modified Eagle medium (DMEM) supplemented with 10 % fetal bovine serum (FBS) and 1 % penicillin/streptomycin solution at 37 ?C in a humidified atmosphere of 5 % CO₂ and 95 % air. Cell invasion and migration were determined using Transwell and wound healing assays, respectively. Real-time quantitative polymerase chain reaction (qRT-PCR) and Western blotting were used for the determination of changes in the levels of expression of Snail, E-cadherin, vimentin, and microRNA-195-5p (miR-195-5p). In vivo tumor growth inhibition was determined 45 days after establishment of GC xenografts in nude mice.

Results: Treatment of MKN28 and NCI-N87 cells with tocotrienolic amide significantly and dose-dependently reduced their invasiveness and migratory capacity (p < 0.05). It also significantly and dose-dependently downregulated the mRNA and protein expressions of Snail and vimentin, but significantly upregulated E-cadherin expression (p < 0.05). The mRNA expression of miR-195-5p was significantly and dose-dependently upregulated in MKN28 and NCI-N87 cells treated with tocotrienolic amide, but was downregulated after transfection with miR-195-5p inhibitor (p < 0.05). Transfection of MKN28 and NCI-N87 cells with miR-195-5p inhibitor significantly and dose-dependently upregulated mRNA and protein expressions of Snail (p < 0.05). Moreover, treatment of GC mice with TCTA led to significant and dose-dependent reduction in tumor weight and volume (p < 0.05).

Conclusion: These results suggest that tocotrienolic amide inhibits the growth and metastasis of GC cells by directly targeting Snail and vimentin genes, and thus can potentially be developed for the management of gastric cancer.

Keywords: Gastric cancer, Metastasis, Protein expression, Tocotrienolic amide, Tumor volume