CAJ | 학술논문

目的探讨以血管内皮生长因子(VEGF)为靶点联合贝伐单抗(Bevacizumab,商品名:阿瓦斯丁,Avastin)和化疗药物诱导多种白血病细胞株凋亡的可行性,研究体外应用VEGF、贝伐单抗和化疗药物Ara-C对白血病细胞株增生、凋亡以及细胞周期的影响.方法应用不同浓度药物作用于体外培养的白血病细胞,CCK-8法检测细胞增生抑制率,流式细胞术(FCM)检测VEGF和贝伐单抗以及联合应用化疗药物后细胞周期和细胞凋亡的变化.结果 VEGF可刺激多种细胞株增生,以U937细胞增生最明显,呈明显的量效关系;FCM检测细胞周期显示VEGF作用组S期细胞较对照组明显增多,而贝伐单抗作用组S期细胞减少;FCM检测显示经VEGF作用组细胞凋亡率较对照组细胞减少,而贝伐单抗作用组细胞凋亡率较对照组增加,但二者与对照组相比差异无统计学意义(P>0.05),联合应用贝伐单抗和Ara-C 48 h后,细胞凋亡率较单用Ara-C组明显升高(P<0.05),联合VEGF、Ara-C组作用48 h后,细胞凋亡率较Ara-C组降低(P<0.05),同时联合应用VEGF、贝伐单抗和Ara-C组细胞凋亡率与Ara-C组差异无统计学意义(P>0.05).结论 VEGF可明显刺激部分白血病细胞增长,抵抗化疗药物诱导的凋亡作用,贝伐单抗可通过中和VEGF而在一定程度上抑制细胞的增生,提高白血病细胞对化疗药物的敏感性.
목적 탐토이혈관내피생장인자(VEGF)위파점연합패벌단항(Bevacizumab,상품명:아와사정,Avastin)화화료약물유도다충백혈병세포주조망적가행성,연구체외응용VEGF、패벌단항화화료약물Ara-C대백혈병세포주증생、조망이급세포주기적영향.방법 응용불동농도약물작용우체외배양적백혈병세포,CCK-8법검측세포증생억제솔,류식세포술(FCM)검측VEGF화패벌단항이급연합응용화료약물후세포주기화세포조망적변화.결과 VEGF가자격다충세포주증생,이U937세포증생최명현,정명현적량효관계;FCM검측세포주기현시VEGF작용조S기세포교대조조명현증다,이패벌단항작용조S기세포감소;FCM검측현시경VEGF작용조세포조망솔교대조조세포감소,이패벌단항작용조세포조망솔교대조조증가,단이자여대조조상비차이무통계학의의(P>0.05),연합응용패벌단항화Ara-C 48 h후,세포조망솔교단용Ara-C조명현승고(P<0.05),연합VEGF、Ara-C조작용48 h후,세포조망솔교Ara-C조강저(P<0.05),동시연합응용VEGF、패벌단항화Ara-C조세포조망솔여Ara-C조차이무통계학의의(P>0.05).결론 VEGF가명현자격부분백혈병세포증장,저항화료약물유도적조망작용,패벌단항가통과중화VEGF이재일정정도상억제세포적증생,제고백혈병세포대화료약물적민감성.
Objective To investigate the potential application of targeting at vascular endothelial growh factor (VEGF) induced apoptosis in leukemic cell lines by combined use of Bevacizumab and chemotherapeutic drug. Methods Leukemic cells were treated with several drugs at different concentrations in culture. The effect of VEGF, Bevacizumab and co-treated with Ara-C on leukemic cells proliferation were evaluated by CCK-8 and apoptosis and cell cycle were detected by flow cytometry (FCM). Results VEGF could enhance the proliferation of leukemic cells and caused a dose-dependent manner on U937 cell. It also increased the percentage of cells in S phase, tested by, and Bevacizumab group was decreased. Apoptotic rate of cells treated with Bevacizumab or co-treated with Bevacizumab and Ara-C for 48 h were significantly higher when compared with control or Ara-C group, respectively (P<0.05), but the apoptotic rate of VEGF group or VEGF and Ara-C group was lower (P>0.05). There was no significant difference in apoptotic rate between control and combined use of VEGF, Bevacizumab and Ara-C group(P>0.05). Conclusion VEGF could enhance the proliferation of some leukemic cells, and may contribute to leukemic cells survival and a resultant resistance to chemotherapy-triggered cell death. The study also showed that leukemic cells growth was significantly inhibited by Bevacizumab through directly against VEGF, and the sensitivity of leukemic cells for chemotherapeutic drug was increased.