中华普通外科杂志
中華普通外科雜誌
중화보통외과잡지
CHINESE JOURNAL OF GENERAL SURGERY
2013年
6期
456-459
,共4页
耿文文%张斌%李丹华%梁新瑞%曹旭晨
耿文文%張斌%李丹華%樑新瑞%曹旭晨
경문문%장빈%리단화%량신서%조욱신
乳腺肿瘤%放射疗法%原癌基因蛋白质c-met
乳腺腫瘤%放射療法%原癌基因蛋白質c-met
유선종류%방사요법%원암기인단백질c-met
Breast neoplasms%Radiotherapy%Proto-oncogene proteins c-met
目的 研究Met抑制剂XL-880对Met阳性乳腺癌MDA-MB-231细胞系放疗增敏作用.方法 依照对细胞不同处理设立对照组、单纯放疗组、XL-880单药组和XL-880联合放疗组.流式细胞术检测不同处理组的细胞早期凋亡率及周期变化,克隆形成试验研究不同处理对肿瘤细胞增殖的影响；Western blot检测细胞周期和凋亡相关蛋白的表达变化和Met通路相关蛋白表达水平的改变.结果 对照组、单纯放疗组、XL-880单药组和XL-880联合放疗组各组克隆数目分别为(41.3±8.2)个、(18.6±2.4)个,(10.6±2.9)个和(0.8±0.2)个,联合组与对照组、单纯放疗组及单药组比较差异有统计学意义(P＜0.05).XL-880处理的MDA-MB-231细胞放疗后48 h,各组G2/M期细胞所占比例分别为(17.3±1.3)％,(20.0±4.0)％,(28.5±3.1)％,(57.0±3.3)％,G2/M期阻滞增加的差异均有统计学意义(均P ＜0.05),Annexin V/PI双染试验中各组细胞的早期凋亡率分别为(7.3±0.9)％、(14.1±0.6)％、(35.5±4.4)％、(48.2±5.3)％,凋亡率明显升高(均P＜0.05).XL-880抑制了放疗后细胞Met磷酸化水平,同时抗凋亡蛋白Bcl-2表达减少,凋亡相关蛋白Caspase-3和PARP蛋白剪切增加.结论 XL-880可通过抑制Met通路进而影响下游Cyclin B1水平而对Met阳性乳腺癌细胞系MDA-MB-231产生放疗增敏作用.
目的 研究Met抑製劑XL-880對Met暘性乳腺癌MDA-MB-231細胞繫放療增敏作用.方法 依照對細胞不同處理設立對照組、單純放療組、XL-880單藥組和XL-880聯閤放療組.流式細胞術檢測不同處理組的細胞早期凋亡率及週期變化,剋隆形成試驗研究不同處理對腫瘤細胞增殖的影響；Western blot檢測細胞週期和凋亡相關蛋白的錶達變化和Met通路相關蛋白錶達水平的改變.結果 對照組、單純放療組、XL-880單藥組和XL-880聯閤放療組各組剋隆數目分彆為(41.3±8.2)箇、(18.6±2.4)箇,(10.6±2.9)箇和(0.8±0.2)箇,聯閤組與對照組、單純放療組及單藥組比較差異有統計學意義(P＜0.05).XL-880處理的MDA-MB-231細胞放療後48 h,各組G2/M期細胞所佔比例分彆為(17.3±1.3)％,(20.0±4.0)％,(28.5±3.1)％,(57.0±3.3)％,G2/M期阻滯增加的差異均有統計學意義(均P ＜0.05),Annexin V/PI雙染試驗中各組細胞的早期凋亡率分彆為(7.3±0.9)％、(14.1±0.6)％、(35.5±4.4)％、(48.2±5.3)％,凋亡率明顯升高(均P＜0.05).XL-880抑製瞭放療後細胞Met燐痠化水平,同時抗凋亡蛋白Bcl-2錶達減少,凋亡相關蛋白Caspase-3和PARP蛋白剪切增加.結論 XL-880可通過抑製Met通路進而影響下遊Cyclin B1水平而對Met暘性乳腺癌細胞繫MDA-MB-231產生放療增敏作用.
목적 연구Met억제제XL-880대Met양성유선암MDA-MB-231세포계방료증민작용.방법 의조대세포불동처리설립대조조、단순방료조、XL-880단약조화XL-880연합방료조.류식세포술검측불동처리조적세포조기조망솔급주기변화,극륭형성시험연구불동처리대종류세포증식적영향；Western blot검측세포주기화조망상관단백적표체변화화Met통로상관단백표체수평적개변.결과 대조조、단순방료조、XL-880단약조화XL-880연합방료조각조극륭수목분별위(41.3±8.2)개、(18.6±2.4)개,(10.6±2.9)개화(0.8±0.2)개,연합조여대조조、단순방료조급단약조비교차이유통계학의의(P＜0.05).XL-880처리적MDA-MB-231세포방료후48 h,각조G2/M기세포소점비례분별위(17.3±1.3)％,(20.0±4.0)％,(28.5±3.1)％,(57.0±3.3)％,G2/M기조체증가적차이균유통계학의의(균P ＜0.05),Annexin V/PI쌍염시험중각조세포적조기조망솔분별위(7.3±0.9)％、(14.1±0.6)％、(35.5±4.4)％、(48.2±5.3)％,조망솔명현승고(균P＜0.05).XL-880억제료방료후세포Met린산화수평,동시항조망단백Bcl-2표체감소,조망상관단백Caspase-3화PARP단백전절증가.결론 XL-880가통과억제Met통로진이영향하유Cyclin B1수평이대Met양성유선암세포계MDA-MB-231산생방료증민작용.
Objective To evaluate the effects of Met inhibitor XL-880 on radiosensitivity of breast cancer cells MDA-MB-231.Methods MDA-MB-231 cell lines were assigned to the following treatment groups:control group,radiation group,XL-880 group and combination group.Cell apoptosis,cell cycle distributions and tumorigenicity were investigated by flow cytometry or clonogenic assay.The expression of apoptosis and cell cycle related proteins (p21,Cyclin B1,Bcl-2,Caspase-3 and PARP),and phosphorylation levels of c-Met were measured by Western blot.Results XL-880 combined with radiation significantly decreased the proliferation activity of MDA-MB-231 cells (P ＜ 0.05).Flow cytometry results showed that the rate of G2/M cell were increased with XL-880 (P ＜ 0.05),and the rate were (17.3 ±1.3) ％,(20.0 ± 4.0) ％,(28.5 ± 3.1) ％,(57.0 ± 3.3) ％,respectively.Annexin V/PI double-staining assay showed that XL-880 obviously induced the apoptosis of MDA-MB-231 cells after radiation (P ＜ 0.05),of which the apoptotic rates were (7.3 ±0.9)％,(14.1 ±0.6)％,(35.5 ±4.4)％,(48.2±5.3)％,respectively.XL-880 downregulated the expressions of Cyclin B1 and anti-apoptosis protein Bcl-2,while promoted the expression of apoptosis related protein cleaved Caspase-3 and PARP.Conclusions XL-880 enhance the radiosensitivity of breast cancer cell MDA-MB-231 by inhibiting Met pathway.
