Effect of NHE1 antisense gene transfection on the biological behavior of SGC-7901 human gastric carcinoma cells

Abstract

AIM:To study the effect of type 1 Na + /H + exchanger (NHE1 ) antisense human gene transfection on the biological behavior of gastric carcinoma cell line SGC-7901. METHODS:Antisense NHE1 eukaryotic expression on vector pcDNA3.1 was constructed by recombinant DNA technique and transfected into gastric carcinoma cell line SGC-7901 with DOTAP liposome transfection method.Morphological changes of cells were observed with optic and electron microscopes. Changes in cell proliferative capacity, apoptosis, intracellular pH (pHi), cell cycle, clone formation in two-layer soft agar, and tumorigenicity in nude mice were examined. RESULTS:Antisense eukaryotic expressing vectors were successfully constructed and transfected into SGC-7901 . The transfectant obtained named 7901 -antisense (7901-AS ) stablely produced antisense NHE1 . There was a significant difference between the pHi of 7901-AS cells (6.77 ± 0.05) and that of 7901-zeo cells and SGC-7901 cells (7.24 ± 0.03 and 7.26 ± 0.03, P < 0.01). Compared with SGC-7901 and 7901-zeo cells, 7901-AS cells mostly showed cell proliferation inhibition, G1/G0 phase arrest, increased cell apoptotic rate, recovery of contact inhibition, and density contact. The tumorigenicity in nude mice and cloning efficiency in the two-layer soft agar were clearly inhibited.

Expression and modulation of Na+/H+ exchanger 1 gene in hepatocellular carcinoma: A potential therapeutic target

“…Our findings were supported by others. Liu 35 showed that the NHE1 antisense gene significantly suppressed cell proliferation and cell cycle of gastric carcinoma cell line SGC‐7901. Perez‐Sala 21 reported that the activation of the NHE1 suppressed apoptosis of HL‐60 cells.…”

Repression of NHE1 Expression by PPARγ Activation Is a Potential New Approach for Specific Inhibition of the Growth of Tumor CellsIn vitroandIn vivo

“…These data support that decrease in NHE1 expression can be specifically induced in tumor cells overexpressing PPARγ, leaving normal cells unaffected. In light of the recent study showing that an antisense therapy targeting NHE1 gene in gastric cancer decreased invasive capacity, and loss of cloning efficiency, and tumorigenicity in nude mice (43), the repressive effect of PPARγ activation on NHE1 expression presents a window of opportunity for exploiting PPARγ agonists for selectively tailoring the expression of NHE1 to achieve a favorable therapeutic response. In addition, synergy between rosiglitazone and platinum-based drugs in several different cancers both in vitro and using transplantable and chemically induced "spontaneous" tumor models was recently reported (44,45).…”

(Patho-)Physiology of Na+/H+ Exchangers (NHEs) in the Digestive System

“…• Gastric cancer Paehler Vor der Nolte et al, 2017 Xue et al, 2011Czepán et al, 2012Liu et al, 2008He et al, 2010;Nagata et al, 2011;Hosogi et al, 2012;Xia et al, 2016;Xie et al, 2017 NHE1 Intestine…”