实用癌症杂志
實用癌癥雜誌
실용암증잡지
The Practical Journal of Cancer
2015年
10期
1439-1442
,共4页
谢建国%钟睿%万爱萍%汪华%康恭礼%何志坚%钟晓鸣
謝建國%鐘睿%萬愛萍%汪華%康恭禮%何誌堅%鐘曉鳴
사건국%종예%만애평%왕화%강공례%하지견%종효명
胰腺肿瘤%放射增敏%PARP抑制剂%DNA修复
胰腺腫瘤%放射增敏%PARP抑製劑%DNA脩複
이선종류%방사증민%PARP억제제%DNA수복
Pancreatic cancer%Radiosensitivity%PARP inhibitor%DNA repair
目的:探讨AG014699提高含BRCA2基因缺陷的胰腺癌细胞放射敏感性的作用机制。方法选择Ca-pan-1和Panc-12种胰腺癌细胞株,分成单纯药物组、单纯放疗组、药物联合放疗组,MTT法检测药物IC50,通过细胞克隆形成率分析细胞存活状态,应用免疫荧光法观察H2Ax的形成。结果单药AG014699(≤10μM)对Capan-1细胞有毒性作用,对Panc-1无效应;放疗联合药物组对Capan-1细胞克隆形成率影响最明显,与单药和单放疗组比较(P<0.05),而该差异在Panc-1细胞中不明显(P>0.05);DNA损伤表现为H2Ax形式,提示DNA双链断裂是细胞死亡的主要模式。结论 AG014699对含有BRCA2基因缺陷的胰腺癌细胞Capan-1有放疗增敏作用。
目的:探討AG014699提高含BRCA2基因缺陷的胰腺癌細胞放射敏感性的作用機製。方法選擇Ca-pan-1和Panc-12種胰腺癌細胞株,分成單純藥物組、單純放療組、藥物聯閤放療組,MTT法檢測藥物IC50,通過細胞剋隆形成率分析細胞存活狀態,應用免疫熒光法觀察H2Ax的形成。結果單藥AG014699(≤10μM)對Capan-1細胞有毒性作用,對Panc-1無效應;放療聯閤藥物組對Capan-1細胞剋隆形成率影響最明顯,與單藥和單放療組比較(P<0.05),而該差異在Panc-1細胞中不明顯(P>0.05);DNA損傷錶現為H2Ax形式,提示DNA雙鏈斷裂是細胞死亡的主要模式。結論 AG014699對含有BRCA2基因缺陷的胰腺癌細胞Capan-1有放療增敏作用。
목적:탐토AG014699제고함BRCA2기인결함적이선암세포방사민감성적작용궤제。방법선택Ca-pan-1화Panc-12충이선암세포주,분성단순약물조、단순방료조、약물연합방료조,MTT법검측약물IC50,통과세포극륭형성솔분석세포존활상태,응용면역형광법관찰H2Ax적형성。결과단약AG014699(≤10μM)대Capan-1세포유독성작용,대Panc-1무효응;방료연합약물조대Capan-1세포극륭형성솔영향최명현,여단약화단방료조비교(P<0.05),이해차이재Panc-1세포중불명현(P>0.05);DNA손상표현위H2Ax형식,제시DNA쌍련단렬시세포사망적주요모식。결론 AG014699대함유BRCA2기인결함적이선암세포Capan-1유방료증민작용。
Objective To investigate radiosensitization mechanism of AG 014699 in BRCA2 deficient pancreatic cancer cells.Methods Pancreatic cancer cells lines were used ,including Capan-1 with mutuated BRCA-2 and Panc-1 with BRCA1/2 wild type.Cell were treated AG014699 and /or radiotherapy (4~10 Gy) then the capability to proliferate was evaluated by colo-ny formation,cell counting and MTT assays .Flow Cytometry were utilized to assess cell respone to AG 014699 plus irradiation.Re-sults AG014699 (≤10 μM)was cytotoxic to Capan-1 cell with mutuated BRCA-2 but not to Panc-1 cell without BRCA1/2 mutations.AG014699 indued DNA double-strand break in Capan-1 cell.Combination treatment with AG014699 plus radiotherapy was more effective than drug alone .Conclusion The rationale of using a PARP inhibitor as radiosensitizer in pancreatic cancer with BRCA2 mutation has been demonstrated .