中国癌症杂志
中國癌癥雜誌
중국암증잡지
CHINA ONCOLOGY
2013年
11期
874-879
,共6页
三阴性乳腺癌%蛋白激酶%迁移%侵袭
三陰性乳腺癌%蛋白激酶%遷移%侵襲
삼음성유선암%단백격매%천이%침습
Triple-negative breast cancer%MAPK%Migration%Invasion
背景与目的：三阴性乳腺癌具有高复发和转移风险，除了化疗，临床上无特定的靶向治疗。因此，研究三阴性乳腺癌复发转移机制对提高患者生存率具有重要意义，本研究旨在探讨丝裂原激活的蛋白激酶(MAPK)信号激活对三阴性乳腺癌细胞迁移和侵袭的影响。方法：首先用细胞划痕和细胞小室(Transwell)试验分析和比较肺高转移三阴性乳腺癌细胞系231-HM及其父代肺低转移细胞系231-p的体外迁移和侵袭性差异；然后用蛋白质印迹法(Western blot)检测转移相关蛋白和MAPK分子激活状态；最后用MAPK抑制剂处理231-p细胞，测定MAPK抑制情况下的细胞迁移、侵袭和相关蛋白变化。结果：与231-p细胞相比，231-HM细胞迁移和侵袭性明显增强；Western blot检测发现，231-HM细胞中促细胞迁移和侵袭蛋白Caveolin-1和β-catenin升高， MAPK通路相关蛋白P38、Erk1/2和MEK的磷酸化水平明显降低；用P38/MAPK磷酸化抑制剂(SB202190)处理231-p细胞后发现，其细胞迁移和侵袭性明显增强，Caveolin-1和β-catenin表达水平上升。结论：MAPK信号激活抑制三阴性乳腺癌的迁移和侵袭。
揹景與目的：三陰性乳腺癌具有高複髮和轉移風險，除瞭化療，臨床上無特定的靶嚮治療。因此，研究三陰性乳腺癌複髮轉移機製對提高患者生存率具有重要意義，本研究旨在探討絲裂原激活的蛋白激酶(MAPK)信號激活對三陰性乳腺癌細胞遷移和侵襲的影響。方法：首先用細胞劃痕和細胞小室(Transwell)試驗分析和比較肺高轉移三陰性乳腺癌細胞繫231-HM及其父代肺低轉移細胞繫231-p的體外遷移和侵襲性差異；然後用蛋白質印跡法(Western blot)檢測轉移相關蛋白和MAPK分子激活狀態；最後用MAPK抑製劑處理231-p細胞，測定MAPK抑製情況下的細胞遷移、侵襲和相關蛋白變化。結果：與231-p細胞相比，231-HM細胞遷移和侵襲性明顯增彊；Western blot檢測髮現，231-HM細胞中促細胞遷移和侵襲蛋白Caveolin-1和β-catenin升高， MAPK通路相關蛋白P38、Erk1/2和MEK的燐痠化水平明顯降低；用P38/MAPK燐痠化抑製劑(SB202190)處理231-p細胞後髮現，其細胞遷移和侵襲性明顯增彊，Caveolin-1和β-catenin錶達水平上升。結論：MAPK信號激活抑製三陰性乳腺癌的遷移和侵襲。
배경여목적：삼음성유선암구유고복발화전이풍험，제료화료，림상상무특정적파향치료。인차，연구삼음성유선암복발전이궤제대제고환자생존솔구유중요의의，본연구지재탐토사렬원격활적단백격매(MAPK)신호격활대삼음성유선암세포천이화침습적영향。방법：수선용세포화흔화세포소실(Transwell)시험분석화비교폐고전이삼음성유선암세포계231-HM급기부대폐저전이세포계231-p적체외천이화침습성차이；연후용단백질인적법(Western blot)검측전이상관단백화MAPK분자격활상태；최후용MAPK억제제처리231-p세포，측정MAPK억제정황하적세포천이、침습화상관단백변화。결과：여231-p세포상비，231-HM세포천이화침습성명현증강；Western blot검측발현，231-HM세포중촉세포천이화침습단백Caveolin-1화β-catenin승고， MAPK통로상관단백P38、Erk1/2화MEK적린산화수평명현강저；용P38/MAPK린산화억제제(SB202190)처리231-p세포후발현，기세포천이화침습성명현증강，Caveolin-1화β-catenin표체수평상승。결론：MAPK신호격활억제삼음성유선암적천이화침습。
Background and purpose:Triple-negative breast cancer (TNBC) possesses high risk of relapse and metastasis. Clinically, there are no speciifc targeted-therapies to TNBC except chemotherapy. Therefore, studying the mechanism of relapse and metastasis has signiifcance to improve the patients’ survival rate. This experiment aimed to study the effect of MAPK activation on migration and invasion of triple-negative breast cancer cells. Methods:Difference of migration and invasion between lung-high metastasis breast cancer cell line 231-HM and its parental cell line 231-p were first examined by cell scratch and transwell;Then, metastasis-associated proteins and MAPK-associated molecules were detected by Western blot; Last, 231-p cells were treated with P38/MAPK inhibitor and used to determine cell migration, invasion, and metastasis-associated proteins thereafter. Results:Compared with the parental cell line 231-p, 231-HM cells displayed obviously higher ability of migration and invasion. With the increased expression of Caveolin-1and β-catenin, the phosphorylation of MAPK-associated molecules including P38, Erk1/2, and MEK was highly decreased. Treatment of 231-p cells with low concentration (10 μmol/L) of the P38/MAPK inhibitor SB202190 increased the migration and invasion of 231-p cells, and the expression of Caveolin-1 andβ-catenin. Conclusion:Activation of MAPK signaling inhibits the migration and invasion of triple-negative breast cancer.
