Upregulation of FAM3B Promotes Cisplatin Resistance in Gastric Cancer by Inducing Epithelial-Mesenchymal Transition
- 22 May 2020
- journal article
- research article
- Published by International Scientific Information, Inc. in Medical Science Monitor
- Vol. 26, e921002
- https://doi.org/10.12659/MSM.921002
Abstract
Background: Cisplatin (CDDP) remains one of the primary chemotherapeutic agents for gastric cancer patients. However, relapse and metastasis are common because of innate and acquired chemo-resistance. Family with sequence similarity 3 (FAM3) is a novel cytokine-like protein that has an important role in tumor progression, but little is known about the role of FAM3B in human gastric cancer CDDP resistance. In this study, we investigated the role of FAM3B in gastric cancer CDDP resistance and reveal the possible underlying mechanism. Material/Methods: We firstly developed a CDDP-resistant gastric cell line AGS/CDDP by treating AGS cells to a continuous exposure of CDDP. The FAM3B levels were compared in these 2 cell lines by quantitative real time polymerase chain reaction (qRT-PCR) and western blotting. Cell viability, apoptosis and epithelial-mesenchymal transition (EMT) related changes were detected after ectopic expression or interfering of FAM3B. Results: We found increased FAM3B expression in AGS/CDDP cells. FAM3B overexpression induced CDDP resistance in AGS cells. Conversely, FAM3B knockdown enhanced CDDP sensitivity of AGS/CDDP cells. Moreover, FAM3B induced EMT in gastric cancer cells by upregulating snail. Inhibition of snail reversed FAM3B-triggered EMT and CDDP resistance. Conclusions: Upregulation of FAM3B triggered CDDP resistance in gastric cancer cells by inducing EMT in a snail-dependent manner, making FAM3B a promising therapeutic target to reverse gastric cancer chemo-resistance.This publication has 35 references indexed in Scilit:
- PEA‑15 contributes to the clinicopathology and AKT‑regulated cisplatin resistance in gastric cancerOncology Reports, 2018
- Distinct mechanisms contribute to acquired cisplatin resistance of urothelial carcinoma cellsOncotarget, 2016
- Cisplatin Resistant Spheroids Model Clinically Relevant Survival Mechanisms in Ovarian TumorsPLOS ONE, 2016
- Epithelial-to-mesenchymal transition is not required for lung metastasis but contributes to chemoresistanceNature, 2015
- Epithelial-to-mesenchymal transition is dispensable for metastasis but induces chemoresistance in pancreatic cancerNature, 2015
- A non-secretory form of FAM3B promotes invasion and metastasis of human colon cancer cells by upregulating Slug expressionCancer Letters, 2013
- Expanding roles of ZEB factors in tumorigenesis and tumor progression2011
- PANDER binds to the liver cell membrane and inhibits insulin signaling in HepG2 cellsFEBS Letters, 2009
- Mechanisms of Glucose-Induced Secretion of Pancreatic-Derived Factor (PANDER or FAM3B) in Pancreatic β-CellsDiabetes, 2005
- Cisplatin: mode of cytotoxic action and molecular basis of resistanceOncogene, 2003