中国癌症杂志
中國癌癥雜誌
중국암증잡지
CHINA ONCOLOGY
2015年
8期
572-578
,共7页
邹存华%王宏%宋冬冬%南平%盛梅
鄒存華%王宏%宋鼕鼕%南平%盛梅
추존화%왕굉%송동동%남평%성매
卵巢癌%尿激酶型纤溶酶原激活剂%细胞外信号调节激酶%丝氨酸/苏氨酸蛋白激酶%P38丝裂原活化蛋白激酶信号通路
卵巢癌%尿激酶型纖溶酶原激活劑%細胞外信號調節激酶%絲氨痠/囌氨痠蛋白激酶%P38絲裂原活化蛋白激酶信號通路
란소암%뇨격매형섬용매원격활제%세포외신호조절격매%사안산/소안산단백격매%P38사렬원활화단백격매신호통로
Ovarian cancer%Urokinase-type plasminogen activator%Extracellular signal-regulated kinase%Serine threonine kinase%P38 mitogen-activated protein kinase signal transduction pathway
背景与目的：P38丝裂原活化蛋白激酶(P38 mitogen-activated protein kinase，P38MAPK)信号通路参与多种肿瘤的发生、发展和转移过程，尿激酶型纤溶酶原激活剂(urokinase-type plasminogen activator，uPA)在肿瘤浸润和转移中发挥着重要作用。本实验研究卵巢癌组织中P38MAPK、细胞外信号调节激酶(extracellular signal-regulated kinase，ERK)、丝氨酸苏氨酸蛋白激酶(serine threonine kinase， AKT)及uPA的表达与临床病理特征的关系，并分析上述蛋白与uPA表达的相关性，探讨P38MAPK信号通路与uPA在卵巢癌细胞及组织中的表达及临床意义。方法：应用免疫组织化学法检测49例卵巢癌组织中uPA、P38MAPK、ERK和AKT蛋白的表达，采用蛋白[质]印迹法(Western blot)检测不同卵巢癌细胞系HO8910、HO-8910PM、SKOV3和CAOV3中uPA和P38MAPK蛋白的表达，使用特异性抑制剂SB203580阻断P38MAPK信号通路后检测uPA蛋白表达水平的变化。结果：uPA、P38MAPK、ERK和AKT蛋白在卵巢癌组织中的表达阳性率分别为61.22%、57.14%、53.06%和55.10%。uPA蛋白的表达与P38MAPK呈正相关(r=0.865，P=0.001)，且与卵巢癌组织的临床病理分期(P=0.029)、分化(P=0.03)和转移程度(P淋巴=0.022，P大网膜=0.012)有关，而与患者的年龄(P=0.754)及组织学类型(P=0.652)无关。ERK、AKT蛋白的表达与卵巢癌淋巴结转移(PERK=0.011，PAKT=0.022)和大网膜转移(PERK=0.006，PAKT=0.000)有关，而与患者的年龄(PERK=0.000，PAKT=0.022)、组织类型(PERK=0.771，PAKT=0.245)及病理分期(PERK=1.000，PAKT=0.254)无关。卵巢癌细胞系HO-8910PM中uPA蛋白的表达水平明显高于HO8910、SKOV3和CAOV3细胞系，使用SB203580阻断P38MAPK信号通路后可降低uPA蛋白的表达，且随着SB203580浓度升高uPA蛋白表达水平逐渐降低。卵巢癌中P38MAPK及uPA蛋白的表达与卵巢癌的预后显著相关(Log-rank=3.897和11.044，P=0.048和0.001)。结论：卵巢癌组织中P38MAPK信号通路处于激活状态；P38MAPK信号通路的激活可上调uPA的表达，促进卵巢癌的恶性进展；P38MAPK信号通路和uPA可能在卵巢癌侵袭和转移的过程中发挥重要作用。P38MAPK和uPA蛋白有望成为卵巢癌预后评估的重要指标。
揹景與目的：P38絲裂原活化蛋白激酶(P38 mitogen-activated protein kinase，P38MAPK)信號通路參與多種腫瘤的髮生、髮展和轉移過程，尿激酶型纖溶酶原激活劑(urokinase-type plasminogen activator，uPA)在腫瘤浸潤和轉移中髮揮著重要作用。本實驗研究卵巢癌組織中P38MAPK、細胞外信號調節激酶(extracellular signal-regulated kinase，ERK)、絲氨痠囌氨痠蛋白激酶(serine threonine kinase， AKT)及uPA的錶達與臨床病理特徵的關繫，併分析上述蛋白與uPA錶達的相關性，探討P38MAPK信號通路與uPA在卵巢癌細胞及組織中的錶達及臨床意義。方法：應用免疫組織化學法檢測49例卵巢癌組織中uPA、P38MAPK、ERK和AKT蛋白的錶達，採用蛋白[質]印跡法(Western blot)檢測不同卵巢癌細胞繫HO8910、HO-8910PM、SKOV3和CAOV3中uPA和P38MAPK蛋白的錶達，使用特異性抑製劑SB203580阻斷P38MAPK信號通路後檢測uPA蛋白錶達水平的變化。結果：uPA、P38MAPK、ERK和AKT蛋白在卵巢癌組織中的錶達暘性率分彆為61.22%、57.14%、53.06%和55.10%。uPA蛋白的錶達與P38MAPK呈正相關(r=0.865，P=0.001)，且與卵巢癌組織的臨床病理分期(P=0.029)、分化(P=0.03)和轉移程度(P淋巴=0.022，P大網膜=0.012)有關，而與患者的年齡(P=0.754)及組織學類型(P=0.652)無關。ERK、AKT蛋白的錶達與卵巢癌淋巴結轉移(PERK=0.011，PAKT=0.022)和大網膜轉移(PERK=0.006，PAKT=0.000)有關，而與患者的年齡(PERK=0.000，PAKT=0.022)、組織類型(PERK=0.771，PAKT=0.245)及病理分期(PERK=1.000，PAKT=0.254)無關。卵巢癌細胞繫HO-8910PM中uPA蛋白的錶達水平明顯高于HO8910、SKOV3和CAOV3細胞繫，使用SB203580阻斷P38MAPK信號通路後可降低uPA蛋白的錶達，且隨著SB203580濃度升高uPA蛋白錶達水平逐漸降低。卵巢癌中P38MAPK及uPA蛋白的錶達與卵巢癌的預後顯著相關(Log-rank=3.897和11.044，P=0.048和0.001)。結論：卵巢癌組織中P38MAPK信號通路處于激活狀態；P38MAPK信號通路的激活可上調uPA的錶達，促進卵巢癌的噁性進展；P38MAPK信號通路和uPA可能在卵巢癌侵襲和轉移的過程中髮揮重要作用。P38MAPK和uPA蛋白有望成為卵巢癌預後評估的重要指標。
배경여목적：P38사렬원활화단백격매(P38 mitogen-activated protein kinase，P38MAPK)신호통로삼여다충종류적발생、발전화전이과정，뇨격매형섬용매원격활제(urokinase-type plasminogen activator，uPA)재종류침윤화전이중발휘착중요작용。본실험연구란소암조직중P38MAPK、세포외신호조절격매(extracellular signal-regulated kinase，ERK)、사안산소안산단백격매(serine threonine kinase， AKT)급uPA적표체여림상병리특정적관계，병분석상술단백여uPA표체적상관성，탐토P38MAPK신호통로여uPA재란소암세포급조직중적표체급림상의의。방법：응용면역조직화학법검측49례란소암조직중uPA、P38MAPK、ERK화AKT단백적표체，채용단백[질]인적법(Western blot)검측불동란소암세포계HO8910、HO-8910PM、SKOV3화CAOV3중uPA화P38MAPK단백적표체，사용특이성억제제SB203580조단P38MAPK신호통로후검측uPA단백표체수평적변화。결과：uPA、P38MAPK、ERK화AKT단백재란소암조직중적표체양성솔분별위61.22%、57.14%、53.06%화55.10%。uPA단백적표체여P38MAPK정정상관(r=0.865，P=0.001)，차여란소암조직적림상병리분기(P=0.029)、분화(P=0.03)화전이정도(P림파=0.022，P대망막=0.012)유관，이여환자적년령(P=0.754)급조직학류형(P=0.652)무관。ERK、AKT단백적표체여란소암림파결전이(PERK=0.011，PAKT=0.022)화대망막전이(PERK=0.006，PAKT=0.000)유관，이여환자적년령(PERK=0.000，PAKT=0.022)、조직류형(PERK=0.771，PAKT=0.245)급병리분기(PERK=1.000，PAKT=0.254)무관。란소암세포계HO-8910PM중uPA단백적표체수평명현고우HO8910、SKOV3화CAOV3세포계，사용SB203580조단P38MAPK신호통로후가강저uPA단백적표체，차수착SB203580농도승고uPA단백표체수평축점강저。란소암중P38MAPK급uPA단백적표체여란소암적예후현저상관(Log-rank=3.897화11.044，P=0.048화0.001)。결론：란소암조직중P38MAPK신호통로처우격활상태；P38MAPK신호통로적격활가상조uPA적표체，촉진란소암적악성진전；P38MAPK신호통로화uPA가능재란소암침습화전이적과정중발휘중요작용。P38MAPK화uPA단백유망성위란소암예후평고적중요지표。
Background and purpose:P38 mitogen-activated protein kinase (P38MAPK) signal transduction pathway is involved in occurrence, development and transfer process in a wide variety of tumors. Urokinase-type plasminogen activator (uPA) plays an important role in tumor invasion and metastasis. This study aimed to explore the clinical signiifcance of the P38MAPK signaling pathway and the expression of uPA in ovarian cancer.Methods:The expressions of uPA, P38MAPK, ERK and AKT were detected in 49 cases of cervical adenocarcinoma by immunohistochemistry. The expressions of uPA and P38MAPK were detected by Western blot in ovarian cancer cell lines HO8910, HO-8910PM, SKOV3 and CAOV3. The changes of uPA and P38MAPK were detected by SB203580, a speciifc inhibitor of P38MAPK signal transduction pathway.Results:The result of immunohistochemical method showed that positive expression rates for uPA, P38MAPK, ERK and AKT were 61.22%, 57.14%, 53.06% and 55.10%, respectively. The expression of the uPA was positively correlated with the P38MAPK (r=0.865,P=0.001), and related with clinicopathologic stage, differentiated degree, lymph node metastasis, but not related with age and histologic type (P>0.05). The expressions of AKT and ERK were related with the lymph node metastasis and greater omentum metastasis(P<0.05), but not related with age and histologic type (P>0.05). The expression of uPA in HO-8910PM was higher than that in ovarian cancer cell lines HO8910, SKOV3 and CAOV3, and the expression of uPA reduced when the P38MAPK signal transduction pathway was cut off by the SB203580. The expressions of P38MAPK and uPA were negatively correlated with the prognosis of ovarian cancer (Log-rank=3.897 and 11.044,P=0.048 and 0.001). Conclusion:The P38MAPK signal transduction pathway was activated in ovarian cancer. The activated P38MAPK signal transduction pathway can raise the expression of uPA, which may contribute to the development of ovarian cancer. The result indicates that the P38MAPK signal transduction pathway and uPA might play an important role in the invasion and metastasis of ovarian cancer. P38MAPK and uPA might be useful markers for evaluating prognosis of ovarian cancer.
