[Inhibitory effect of N-terminal 24 amino acids of the p55 gamma, a regulatory subunit of phosphoinositide 3-kinase, on proliferation of colon carcinoma cell line HT29].

ABSTRACT

BACKGROUND & OBJECTIVE: p55 gamma is one of the regulatory subunits of phosphoinositide 3-kinase (PI3K), which plays an important role in the regulation of PI3K activity. This study was to explore the inhibitory effect of the N-terminal 24 amino acids of the p55 gamma on proliferation of colon carcinoma cell line HT29. METHODS: Ad-N24p55-GFP, containing N-terminal 24 amino acids of the p55 gamma, and control vector Ad-GFP were constructed, and used to infect HT29 cells. The cell cycle progression was detected using flow cytometry. DNA synthesis was analyzed using the BrdU/PI method. The nude mice model bearing HT29 xenograft tumors was used to study the effect of Ad-N24p55-GFP against the tumor. RESULTS: Compared with cells infected with Ad-GFP, cells infected with Ad-N24p55-GFP at the G0/G1 phase were increased from 65.11% to 73.39% P < 0.05, and cells at S and G2/M phases were decreased from 17.37% to 15.08% and from 17.51% to 11.13%, respectively; BrdU-positive cells were decreased from 24.82% to 9.27%. In the nude mice model, the tumor growth was inhibited after the administration of Ad-N24p55-GFP. The tumor weight was (0.32+/-0.08)g vs. (10.67+/-0.3)g and (0.72+/-0.28)g in the Ad-N24P55-GFP group,the blank control group and the Ad-GFP group, respectively. CONCLUSION: In HT29 cells, overexpression of the N-terminal 24 amino acids of the p55 gamma can induce cell cycle arrest, inhibit DNA synthesis and inhibit tumor growth in the nude mice model of HT29 xenograft tumors.