CAJ | 학술논문

目的：观察过氧化物酶体增殖因子激活受体α（ PPARα）激动剂苯扎贝特联用顺铂对肺腺癌 A549细胞增殖抑制和诱导凋亡的协同效应及可能机制。方法采用CCK8法测定不同浓度苯扎贝特处理A549细胞的生长曲线，观察苯扎贝特、顺铂及两药联用对A549细胞的生长抑制作用，并应用中效原理评价两药联用效应；采用流式细胞技术分析苯扎贝特与顺铂联用对细胞凋亡的诱导作用，并通过qRT-PCR检测A549细胞中VEGF和HIF-1αmRNA的表达变化。结果苯扎贝特联合顺铂呈现明显协同抑制效应，两药联用时IC50值为15.92μmol·L-1，当苯扎贝特浓度小于588μmol·L-1，顺铂浓度小于206μmol·L-1，CI值小于1，即两药合用均产生协同作用。联合用药组细胞凋亡率明显高于单药组（ P<0.05），并且联合用药组较单药组显著下调VEGF和HIF-1α mRNA的表达，差异有统计学意义（ P<0.05）。结论苯扎贝特联合顺铂对肺癌细胞具有协同抑制效应，并可有效诱导细胞凋亡，其机制可能与下调VEGF和HIF-1α的表达有关。
목적：관찰과양화물매체증식인자격활수체α（ PPARα）격동제분찰패특련용순박대폐선암 A549세포증식억제화유도조망적협동효응급가능궤제。방법채용CCK8법측정불동농도분찰패특처리A549세포적생장곡선，관찰분찰패특、순박급량약련용대A549세포적생장억제작용，병응용중효원리평개량약련용효응；채용류식세포기술분석분찰패특여순박련용대세포조망적유도작용，병통과qRT-PCR검측A549세포중VEGF화HIF-1αmRNA적표체변화。결과분찰패특연합순박정현명현협동억제효응，량약련용시IC50치위15.92μmol·L-1，당분찰패특농도소우588μmol·L-1，순박농도소우206μmol·L-1，CI치소우1，즉량약합용균산생협동작용。연합용약조세포조망솔명현고우단약조（ P<0.05），병차연합용약조교단약조현저하조VEGF화HIF-1α mRNA적표체，차이유통계학의의（ P<0.05）。결론분찰패특연합순박대폐암세포구유협동억제효응，병가유효유도세포조망，기궤제가능여하조VEGF화HIF-1α적표체유관。
Objective To observe the effects of peroxisome proliferator-activated receptorα( PPARα)agonist bezaf-ibrate combinated with cisplatin( DDP)on proliferation and apoptosis of lung adenocarcinoma( AC)A549 cell and the pos-sible mechanism. MetHods CCK8 kit assay was used to detect growth inhibiton curve of A549 cells treated with various concentrations of bezafibrate. The median-effect method was used to evaluate the combination effect. Cell apoptosis was e-valuated with flow cytometry,and the expression of VEGF and HIF-1αmRNA were analyzed using real-time PCR( qRT-PCR). Results Bezafibrate combinated with DDP showed significately synergy inhibition effect,and the IC50 was 15. 92μmol·L-1 when the two agents were combined. The combination index(CI)was less than 1 when the concentration of bez-afibrate<588 μmol·L-1 and cisplatin<206 μmol·L-1 ,namely two drugs combination showed synergy effect. The cell apoptosis rate of A549 cells was significately higher than single drug group(P<0. 05). The expression level of VEGF and HIF-1α mRNA were significately lower in combination group than in bezafibrate or cisplatin group(P<0. 05). CoNclu-sioN Our results demonstrated that bezafibrate combinated with cisplatin showed synergy inhibition effect on lung AC, which may be related with the down-expression of VEGF and HIF-1α.