Open AccessSilencing of galectin‐3 changes the gene expression and augments the sensitivity of gastric cancer cells to chemotherapeutic agents
Author(s) -
Cheong TeakChin,
Shin JiYoung,
Chun KyungHee
Publication year - 2010
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2009.01364.x
Subject(s) - gene silencing , survivin , xiap , cancer research , biology , small interfering rna , cell cycle , cyclin d1 , cancer cell , cancer , gene expression , apoptosis , cell growth , programmed cell death , gene , caspase , transfection , genetics
Galectin‐3 is known to modulate cell proliferation and apoptosis and is highly expressed in human cancers, but its function in gastric cancer is still controversial. Here, we examined the role of galectin‐3 in gastric cancer cells by silencing it with synthetic double‐stranded siRNA. After silencing of galectin‐3, cell numbers decreased and cell shape changed. Galectin‐3 siRNA treatment also induced G 1 arrest. DNA microarray analysis was used to assess changes in gene expression following galectin‐3 silencing. We found that silencing of galectin‐3 caused changes in gene expression. RT‐PCR and real‐time PCR were utilized for validation of the changes found in microarray studies. Western blot analysis confirmed changes in the expression of proteins of interest: cyclin D1, survivin, XIAP, XAF, PUMA, and GADD45α. Generally, it tended to increase the expression of several pro‐apoptotic genes, and to decrease the expression of cell cycle progressive genes. We also confirmed that changes in the expression of these genes were caused by galectin‐3 overexpression. Finally, we demonstrated that silencing of galectin‐3 enhanced apoptosis induction with chemotherapeutic agents by further reducing the expression of anti‐apoptotic and/or cell survival molecules such as survivin, cyclin D1, and XIAP, and increasing the expression of pro‐apoptotic XAF‐1. We conclude that galectin‐3 is involved in cancer progression and malignancy by modulating the expression of several relevant genes, and inhibition of galectin‐3 may be an approach to improve chemotherapy of gastric cancers. ( Cancer Sci 2009)