Effects of regulating PI3K/Akt signaling pathway on xenograft model of hemangioma in nude mice

Abstract

Objective To explore the expressions of phosphatidylinositol 3-kinase p85(PI3Kp85) and protein kinase B(Akt) in nude mice model of human hemangioma xenograft and examine the role of PI3K/Akt signaling pathway in evolution process of hemangioma in children. Methods The surgical specimens of proliferating hemangioma were harvested from a male 3-month-old infant. The tissues were sliced into small pieces 5 mm 4 mm 3 mm in size and grafted subcutaneously into nude mice. After growing for 45 days, a total of 48 cases of successful xenograft specimens were randomized into 3 groups: 0.05 ml saline was intratumorally injected for each tumor in control group, 0.05 ml insulin-like growth factor(0.5 μmol/L)intratumorally injected for each tumor in positive control group and 0.05 ml LY294002(25 μmol/L)was intratumorally injected for each tumor in negative control group. At the day of injection and 3 days, 1 week and 2 weeks post-injection, the morphological changes of hemangioma xenografts were visually observed and their structural changes observed microscopically. The expressions of PI3Kp85, p-Akt protein were determined by immunohistochemistry. And the expressions of PI3Kp85 mRNA and p-Aktm RNA were observed by reverse transcription-polymerase chain reaction(RT-PCR). Results The positive expression rates of PI3Kp85 and p-Akt were 100% in control and positive control groups. And the positive expression rates were 80.00% and 86.67% in negative control group. The stains of PI3Kp85 and p-Akt became weaker significantly in negative control group. And significant differences in PI3Kp85 and p-Akt stains existed between negative control and control groups(P<0.05 or 0.01) and then xenograft specimens showed regression. The stains of PI3Kp85 and p-Akt turned stronger significantly in positive control group. Significant differences of PI3Kp85 and p-Akt stains existed between positive control and control groups(P<0.05 or 0.01). The xenograft specimens showed proliferation. And the expression levels of PI3Kp85 and p-Akt had positive correlations. Conclusions PI3K/Akt signal pathway is probably participating in regulating the apoptosis of hemangioma endothelial cells in nude mice model with human hemangioma xenograft. And LY294002 and insulin-like growth factor may induce tumor regression and proliferation by intervening the corresponding targets in PI3K/Akt signaling pathway. Key words: Hemangioma; Models, animal; Signal transduction; Gene expression regulation