中国神经精神疾病杂志
中國神經精神疾病雜誌
중국신경정신질병잡지
CHINESE JOURNAL OF NERVOUS AND MENTAL DISEASES
2010年
2期
104-107
,共4页
宋云朋%刘哲%钟跃%康春生%许鹏%韩磊%张安玲%王广秀%贾志凡%浦佩玉
宋雲朋%劉哲%鐘躍%康春生%許鵬%韓磊%張安玲%王廣秀%賈誌凡%浦珮玉
송운붕%류철%종약%강춘생%허붕%한뢰%장안령%왕엄수%가지범%포패옥
胶质瘤%PI3K抑制剂%PTEN
膠質瘤%PI3K抑製劑%PTEN
효질류%PI3K억제제%PTEN
Glioma%Phosphatidylinositol 3-Kinase inhibitor%PTEN
目的 本研究旨在观察磷脂酰肌醇3-激酶 (PI3K)抑制剂LY294002联合含PTEN基因的重组腺病毒(Ad-PTEN)对人脑胶质瘤裸鼠移植瘤的抗肿瘤作用,初步探讨其可能的作用机制.方法 将实验动物24只随机分为4组,即胶质瘤模型给予DMSO对照组、空载对照组、LY294002治疗组及LY294002与Ad-PTEN联合治疗组.皮下接种LN229人脑胶质瘤细胞建立胶质瘤裸鼠皮下移植瘤模型,定期测量动物体质量及肿瘤直径;应用免疫组化法检测肿瘤细胞的PTEN、p-Akt、PCNA、CyclinD1、Caspase-3、MMP-2、p-FAK的表达水平.结果 联合治疗组对人脑胶质瘤裸鼠移植瘤抑制作用较对照组及LY294002治疗组均明显增强(均 P <0.01) ;与对照组及LY294002治疗组比较联合治疗组Caspase-3、PTEN表达显著升高(均 P <0.05),p-Akt、CyclinD1、MMP2、p-FAK的表达均显著下降(均 P <0.05).结论 LY294002与Ad-PTEN联合治疗可以提高对裸鼠移植人脑胶质瘤的抑制作用.
目的 本研究旨在觀察燐脂酰肌醇3-激酶 (PI3K)抑製劑LY294002聯閤含PTEN基因的重組腺病毒(Ad-PTEN)對人腦膠質瘤裸鼠移植瘤的抗腫瘤作用,初步探討其可能的作用機製.方法 將實驗動物24隻隨機分為4組,即膠質瘤模型給予DMSO對照組、空載對照組、LY294002治療組及LY294002與Ad-PTEN聯閤治療組.皮下接種LN229人腦膠質瘤細胞建立膠質瘤裸鼠皮下移植瘤模型,定期測量動物體質量及腫瘤直徑;應用免疫組化法檢測腫瘤細胞的PTEN、p-Akt、PCNA、CyclinD1、Caspase-3、MMP-2、p-FAK的錶達水平.結果 聯閤治療組對人腦膠質瘤裸鼠移植瘤抑製作用較對照組及LY294002治療組均明顯增彊(均 P <0.01) ;與對照組及LY294002治療組比較聯閤治療組Caspase-3、PTEN錶達顯著升高(均 P <0.05),p-Akt、CyclinD1、MMP2、p-FAK的錶達均顯著下降(均 P <0.05).結論 LY294002與Ad-PTEN聯閤治療可以提高對裸鼠移植人腦膠質瘤的抑製作用.
목적 본연구지재관찰린지선기순3-격매 (PI3K)억제제LY294002연합함PTEN기인적중조선병독(Ad-PTEN)대인뇌효질류라서이식류적항종류작용,초보탐토기가능적작용궤제.방법 장실험동물24지수궤분위4조,즉효질류모형급여DMSO대조조、공재대조조、LY294002치료조급LY294002여Ad-PTEN연합치료조.피하접충LN229인뇌효질류세포건립효질류라서피하이식류모형,정기측량동물체질량급종류직경;응용면역조화법검측종류세포적PTEN、p-Akt、PCNA、CyclinD1、Caspase-3、MMP-2、p-FAK적표체수평.결과 연합치료조대인뇌효질류라서이식류억제작용교대조조급LY294002치료조균명현증강(균 P <0.01) ;여대조조급LY294002치료조비교연합치료조Caspase-3、PTEN표체현저승고(균 P <0.05),p-Akt、CyclinD1、MMP2、p-FAK적표체균현저하강(균 P <0.05).결론 LY294002여Ad-PTEN연합치료가이제고대라서이식인뇌효질류적억제작용.
Objective Increasing evidence suggest that aberrant activation of PI3K/Akt is involved in many human cancers, and that inhibition of the PI3K/Akt pathway might be a promising strategy for cancer therapy. The study is to evaluate the effects of combined therapy of PI3K inhibitor (LY294002) and Ad-PTEN in athymic mice xenogeneic transplant model of human glioma and to reveal the possible mechanisms involved.Methods Twenty-four athymic mice were randomly divided into 4 groups (DMSO、Ad-vector plus DMSO、LY294002 alone and Ad-PTEN plus LY294002), and were treated, respectively. Athymic mice xenogeneic transplant model was established by inoculation (sc) with LN229 glioma cells. Body mass (BM) and diameter of tumor mass were measured. Furthermore, The protein expressions of PTEN、p-Akt、CyclinD1、Caspase-3、MMP-2、p-FAK in tumor tissues were analyzed with immunohistochemistry.Results The tumor-inhibiting rate of was significantly higher in Ad-PTEN plus LY294002 than in the LY294002 alone (92.46 vs 65.59%)( P <0.05).The protein expressions of PTEN and Caspase-3 were significantly higher, while PCNA、CyclinD1、bcl-2 and MMP-2、p-FAK was significantly lower in Ad-PTEN plus LY294002 group than in the other three groups ( P <0.05).Conclusions LY294002 plus Ad-PTEN achieve better outcome than either alone in treating glioma possibly through enhancement of the inhibitory action of PI3K/Akt pathway and Ad-PTEN pathway.