中国肿瘤临床
中國腫瘤臨床
중국종류림상
CHINESE JOURNAL OF CLINICAL ONCOLOGY
2013年
5期
243-247
,共5页
王林%张振东%解海%李大祥%张乐%孙敬岩
王林%張振東%解海%李大祥%張樂%孫敬巖
왕림%장진동%해해%리대상%장악%손경암
Src激酶抑制剂%乳腺癌%肿瘤转移
Src激酶抑製劑%乳腺癌%腫瘤轉移
Src격매억제제%유선암%종류전이
Src kinase inhibitor%breast cancer%tumor metastasis
目的:探讨Src激酶抑制剂PP2在乳腺癌MCF-7细胞转移中的作用和机制.方法:乳腺癌MCF-7细胞经PP2作用48 h后,检测肿瘤细胞体外粘附、侵袭能力的改变,细胞周期的改变,Western blot及Real-time PCR试验检测肿瘤细胞转移相关基因表达的变化,报告基因试验检测AP-1和NF-κB启动子活性的变化.结果:PP2可抑制MCF-7细胞中Src激酶活性,2.5μM和5μM PP2作用后,肿瘤细胞粘附能力下降63.4%和34.7%;侵袭能力下降44.3%和20.2%;细胞周期显著阻滞在G0/G1期;CD44、MMP-2/9以及p-β-catenin表达显著下降,E-cadherin表达显著升高;AP-1启动子活性下降64.5%和37.9%,NF-κB启动子活性下降55.7%和31.8%.结论:Src激酶与乳腺癌MCF-7细胞肿瘤转移能力密切相关,阻断Src激酶活性可抑制肿瘤细胞转移能力.
目的:探討Src激酶抑製劑PP2在乳腺癌MCF-7細胞轉移中的作用和機製.方法:乳腺癌MCF-7細胞經PP2作用48 h後,檢測腫瘤細胞體外粘附、侵襲能力的改變,細胞週期的改變,Western blot及Real-time PCR試驗檢測腫瘤細胞轉移相關基因錶達的變化,報告基因試驗檢測AP-1和NF-κB啟動子活性的變化.結果:PP2可抑製MCF-7細胞中Src激酶活性,2.5μM和5μM PP2作用後,腫瘤細胞粘附能力下降63.4%和34.7%;侵襲能力下降44.3%和20.2%;細胞週期顯著阻滯在G0/G1期;CD44、MMP-2/9以及p-β-catenin錶達顯著下降,E-cadherin錶達顯著升高;AP-1啟動子活性下降64.5%和37.9%,NF-κB啟動子活性下降55.7%和31.8%.結論:Src激酶與乳腺癌MCF-7細胞腫瘤轉移能力密切相關,阻斷Src激酶活性可抑製腫瘤細胞轉移能力.
목적:탐토Src격매억제제PP2재유선암MCF-7세포전이중적작용화궤제.방법:유선암MCF-7세포경PP2작용48 h후,검측종류세포체외점부、침습능력적개변,세포주기적개변,Western blot급Real-time PCR시험검측종류세포전이상관기인표체적변화,보고기인시험검측AP-1화NF-κB계동자활성적변화.결과:PP2가억제MCF-7세포중Src격매활성,2.5μM화5μM PP2작용후,종류세포점부능력하강63.4%화34.7%;침습능력하강44.3%화20.2%;세포주기현저조체재G0/G1기;CD44、MMP-2/9이급p-β-catenin표체현저하강,E-cadherin표체현저승고;AP-1계동자활성하강64.5%화37.9%,NF-κB계동자활성하강55.7%화31.8%.결론:Src격매여유선암MCF-7세포종류전이능력밀절상관,조단Src격매활성가억제종류세포전이능력.
Objective:This study aimed to investigate the effects of Src kinase inhibitor PP2 in the metastasis of human breast cancer MCF-7 cells and its related mechanisms. Methods:MCF-7 cells were treated with PP2 for 48 h to detect the changes in cell adhesion, invasion, and cycle. In particular, western blot and real-time polymerase chain reaction assays were performed to determine the expression of metastasis-related gene. Reporter gene assay was performed to examine the promoter transcriptional activity of nuclear factor kappaB (NF-κB) and transcription factor AP-1 (AP-1). Results:PP2 could downregulate Src activities in MCF-7 cells after these cells were treated with PP2 for 48 h. After these cells were treated with 2.5 and 5 μM PP2, the cell adhesion potentials of MCF-7 cells were decreased by 63.4%and 34.7%, respectively. The cell invasion potentials were also decreased by 44.3%and 20.2%, respectively. The cell cycle was inhibited at the G0/G1 phase. CD44, MMP-2/9, and p-β-catenin expressions were decreased, whereas E-cadherin expression was increased. The promoter transcriptional activities of AP-1 were decreased by 64.5%(2.5 μM PP2) and 37.9%(5 μM PP2). The promoter transcriptional activities of NF-κB were also decreased by 55.7%(2.5 μM PP2) and 31.8%(5 μM PP2). Conclusion:A close relationship was found between Src kinase and the metastasis potential of human breast cancer MCF-7 cells. The inhibition of Src kinase activity could suppress tumor metastasis.