中华肿瘤杂志
中華腫瘤雜誌
중화종류잡지
CHINESE JOURNAL OF ONCOLOGY
2009年
8期
577-581
,共5页
王伟%陈平%李军利%裴艳芳%双庆翠%刘彩虹%蔡珊%刘绍坤%诸兰艳%周锐
王偉%陳平%李軍利%裴豔芳%雙慶翠%劉綵虹%蔡珊%劉紹坤%諸蘭豔%週銳
왕위%진평%리군리%배염방%쌍경취%류채홍%채산%류소곤%제란염%주예
肺肿瘤%A549-DDP细胞%Tumstatin%Akt%ERK
肺腫瘤%A549-DDP細胞%Tumstatin%Akt%ERK
폐종류%A549-DDP세포%Tumstatin%Akt%ERK
Lung neoplasms%A549-DDP cell line%Tumstatin%Akt%ERK
目的 观察Tumstatin185～191单药及联合顺铂(DDP)对肺腺癌耐药细胞株A549-DDP增殖和凋亡的影响,并探讨其联合作用的机制.方法 以不同浓度的Tumstatin185～191单药、DDP单药及Tumstatin185～191联合DDP干预A549-DDP细胞,采用四甲基偶氮唑蓝(MTT)法测定细胞的增殖情况,流式细胞术检测细胞凋亡的变化,Western blot法检测A549-DDP细胞内p-Akt和p-ERK蛋白的表达水平.结果 Tumstatin185～191对A549-DDP细胞的增殖具有抑制作用,其半数抑制浓度(IC50)为80.25 μmol/L.DDP单药对A549-DDP的IC50为77.16 μmol/L,当DDP与20 μmol/L的Tumstatin185～191联合使用时,DDP对A549-DDP细胞的IC50为57.97 μmol/L,耐药逆转指数为1.33;当DDP与40 μmol/L的Tumstatin185～191联合使用时,DDP对A549-DDP细胞的IC50为26.40 μmol/L,耐药逆转指数为2.92.两药联合使用时,A549-DDP细胞的早期凋亡率为19.5%±1.1%,较DDP单药(13.3%±1.5%)和Tumstatin185～191单药使用时的早期凋亡率(10.2%±2.0%)显著增加(F=4.09,P<0.05).Tumatatin185～191能显著抑制A549-DDP细胞内p-Akt和P-ERK蛋白的表达,但如与DDP联合使用,并不能增加Tumstatin185～191对P-ERK和p-Akt蛋白表达的抑制效应.结论 Tumstatin185～191能抑制肺腺癌耐药细胞株A549-DDP的增殖、促进凋亡,并部分逆转A549-DDP细胞对DDP的化疗耐药;其作用机制可能与Tumstatin185～191能下调A549-DDP细胞内p-Akt和p-ERK蛋白的表达有关.
目的 觀察Tumstatin185～191單藥及聯閤順鉑(DDP)對肺腺癌耐藥細胞株A549-DDP增殖和凋亡的影響,併探討其聯閤作用的機製.方法 以不同濃度的Tumstatin185～191單藥、DDP單藥及Tumstatin185～191聯閤DDP榦預A549-DDP細胞,採用四甲基偶氮唑藍(MTT)法測定細胞的增殖情況,流式細胞術檢測細胞凋亡的變化,Western blot法檢測A549-DDP細胞內p-Akt和p-ERK蛋白的錶達水平.結果 Tumstatin185～191對A549-DDP細胞的增殖具有抑製作用,其半數抑製濃度(IC50)為80.25 μmol/L.DDP單藥對A549-DDP的IC50為77.16 μmol/L,噹DDP與20 μmol/L的Tumstatin185～191聯閤使用時,DDP對A549-DDP細胞的IC50為57.97 μmol/L,耐藥逆轉指數為1.33;噹DDP與40 μmol/L的Tumstatin185～191聯閤使用時,DDP對A549-DDP細胞的IC50為26.40 μmol/L,耐藥逆轉指數為2.92.兩藥聯閤使用時,A549-DDP細胞的早期凋亡率為19.5%±1.1%,較DDP單藥(13.3%±1.5%)和Tumstatin185～191單藥使用時的早期凋亡率(10.2%±2.0%)顯著增加(F=4.09,P<0.05).Tumatatin185～191能顯著抑製A549-DDP細胞內p-Akt和P-ERK蛋白的錶達,但如與DDP聯閤使用,併不能增加Tumstatin185～191對P-ERK和p-Akt蛋白錶達的抑製效應.結論 Tumstatin185～191能抑製肺腺癌耐藥細胞株A549-DDP的增殖、促進凋亡,併部分逆轉A549-DDP細胞對DDP的化療耐藥;其作用機製可能與Tumstatin185～191能下調A549-DDP細胞內p-Akt和p-ERK蛋白的錶達有關.
목적 관찰Tumstatin185～191단약급연합순박(DDP)대폐선암내약세포주A549-DDP증식화조망적영향,병탐토기연합작용적궤제.방법 이불동농도적Tumstatin185～191단약、DDP단약급Tumstatin185～191연합DDP간예A549-DDP세포,채용사갑기우담서람(MTT)법측정세포적증식정황,류식세포술검측세포조망적변화,Western blot법검측A549-DDP세포내p-Akt화p-ERK단백적표체수평.결과 Tumstatin185～191대A549-DDP세포적증식구유억제작용,기반수억제농도(IC50)위80.25 μmol/L.DDP단약대A549-DDP적IC50위77.16 μmol/L,당DDP여20 μmol/L적Tumstatin185～191연합사용시,DDP대A549-DDP세포적IC50위57.97 μmol/L,내약역전지수위1.33;당DDP여40 μmol/L적Tumstatin185～191연합사용시,DDP대A549-DDP세포적IC50위26.40 μmol/L,내약역전지수위2.92.량약연합사용시,A549-DDP세포적조기조망솔위19.5%±1.1%,교DDP단약(13.3%±1.5%)화Tumstatin185～191단약사용시적조기조망솔(10.2%±2.0%)현저증가(F=4.09,P<0.05).Tumatatin185～191능현저억제A549-DDP세포내p-Akt화P-ERK단백적표체,단여여DDP연합사용,병불능증가Tumstatin185～191대P-ERK화p-Akt단백표체적억제효응.결론 Tumstatin185～191능억제폐선암내약세포주A549-DDP적증식、촉진조망,병부분역전A549-DDP세포대DDP적화료내약;기작용궤제가능여Tumstatin185～191능하조A549-DDP세포내p-Akt화p-ERK단백적표체유관.
Objective To investigate the effects and related mechanisms of Tumstatin 185-191 as a single agent or in combination with cisplatin on proliferation and apoptosis in a cisplatin-reslstant hnman lung edenocarcinoma cell line A549-DDP cells. Methods A549-DDP cells were treated with Tumstatin185-191 and cisplatin at varying concertrations. Cell viability was assessed by a modified 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyhetrazolium bromide (MTT) assay. 50% inhibiting concentration (IC50) values of the chemotherapeutic drugs were analyzed by MTT assay. Cell apoptosis was measured by flow cytometry. The activation of Akt and ERK was evaluated by Western blotting. Results Tumstatin185-191 inhibited the proliferation of A549-DDP cells and its IC50 value was 80.25 μmol/L. After cotreatment with 20 μmol/L Tum185-191, the IC50 value of eisplatin in A549-DDP cells reduced from 77.16 μmol/L to 57.97 μmol/L, the reverse index was 1.33, while with 40 μmol/L Tumstatin185-191 the IC50 was reduced from 77.16 to 26.40 μmol/L and the reverse index was 2.92. The early apoptosis rate was 19.5% ± 1. 1% in the cotreatment group, while 13.3% ±1.5% in cisplatin group and 10.2% ±2.0% in Tum185-191 group ( F = 4.09, P <0.05). The levels of phospho-Akt (p-Akt) and phospho-ERK (p-ERK) in the A549-DDP cells were remarkably lower after treatement with Tumstatin 185-191. The Tumstatin 185-191 treatment alone or in combination with cisplatin had a similar effect on the protein levels of p-Akt and p-ERK in A549-DDP cells. Conclusion Our data suggest that Tumstatin185-191 may promote apoptosis, downregulate proliferation and partly reverse the drug resistance of A549-DDP cells to eisplatin. The effects induced by Tum185-191 may be mediated through inactivation of the Akt and ERK pathways.
