Abstract
AbstractGastric cancer is still a major health problem worldwide due to its frequency, poor prognosis and limited treatment options. To study the inhibitory effect of nuclear transcription factor kappa B(NF-κB) antisense oligodeoxynucleotide(ASODN) on the growth and tumorgenesis of human gastric cancer, we synthesis and transfect ASODN of NF-κB/P65 to gastric cancer cell line. The effect of ASODN of NF-κB/P65 on the proliferation of gastric cancer cells was measured by MTT method. The subcutaneous xenograft model of human gastric cancer was established in nude mice and the tumor growth curve was observed. The cell proliferation was significantly inhibited in P65 ASODN transfected group in vitro (P<0.05). In vivo, tumor formation test showed that the tumor volume in nude mice in ASODN group was obviously smaller than in other groups (P<0.05), the apoptosis index (AI) was significantly higher (P<0.001). Stimultaneously, MVD in ASODN group was markedly lower than in other groups (P<0.01). Our findings suggest that P65 ASODN can inhibit gastric cancer cells proliferation and tumorgenesis by inducing cell apoptosis and inhibiting tumor angiogenesis. NF-κB can be used as a new biological therapeutic target of gastric cancer.
Highlights
NF-κB is activated by a variety of cancer-promoting agents[1]
P65 ASODN suppresses gastric tumor growth in vivo Because it showed that P65 ASODN has a significant inhibitory effect on the growth of gastric cancer cells in vitro, we studied the effect of ASODN on tumor growth in vivo
It was suggested that P65 ASODN could inhibit gastric cancer cell proliferation, it maybe related to the decreased expression of P65
Summary
Recent studies showed that as a multifunctional factor, NF-κB involved in a variety of physiological and pathological processes such as immunity, inflammation, gene expression, cancer cell migration invasion, cell apoptosis and proliferation[2,3,4,5,6].The mechanism of NF-κB activation in tumor cells is not well elucidated, but it is apparently complex and varies in different tumor types[7]. NF-κB constitutive activation was identified in some cancer cells such as breast cancer, liver cancer, prostate cancer, pancreatic cancer, and gastric cancer[8]. We have previously shown that there exists NF-κB constitutive activation in gastric cancer cell [9,10]. We examined the impact that antisense oligonucleotide NF-κB on cell proliferation and tumorgenesis of gastric cancer in nude mice
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