重组人P53腺病毒联合紫杉醇对宫颈癌HeLa细胞的抑制作用及其机制  

Inhibitory effect of recombinant human adenovirus-P53combined with paclitaxel on human cervical cancer HeLa cells and its mechanism

作　　者：郑小莉[1] 王婷婷 付敏[3] 周健[3] 刘福民[4] 

机构地区：[1]徐州医学院附属徐州市立医院妇产科,江苏徐州221002 [2]徐州市第六人民医院妇产科,江苏徐州221006 [3]徐州市妇幼保健院妇科,江苏徐州221009 [4]徐州医学院附属医院妇产科,江苏徐州221002

出　　处：《中国肿瘤生物治疗杂志》2013年第2期192-196,共5页Chinese Journal of Cancer Biotherapy

基　　金：江苏省卫生厅康莱特临床肿瘤研究基金资助项目(No.P200943)~~

摘　　要：目的:探讨重组人P53腺病毒(recombinant human adenovirus-P53,rAd-P53)联合紫杉醇对宫颈癌HeLa细胞增殖、凋亡及血管内皮生长因子(vascular endothelial growth factor,VEGF)表达的影响。方法:MTT法检测紫杉醇、rAd-P53单独或联合应用后HeLa细胞的增殖;DAPI染色法检测紫杉醇、rAd-P53单独或联合作用48 h后HeLa细胞的凋亡;Western blotting法检测紫杉醇、rAd-P53单独或联合作用后HeLa细胞VEGF的表达情况。结果:紫杉醇、rAd-P53单独或联合作用24～72 h均能抑制HeLa细胞的增殖,抑制作用具有时效和量效关系,且联合用药组对HeLa细胞的抑制率显著高于单用紫杉醇组及rAd-P53组(P<0.05);联合作用时的相互作用系数(coefficient of drug interaction,CDI)均<1,说明两者具有协同作用;rAd-P53(5×107VP/ml)联合紫杉醇(3μg/ml)作用48 h后,对HeLa细胞增殖的抑制率高于两药单用组[(54.0±0.92)%vs(31.8±0.58)%、(27.2±0.55)%,P<0.05]。联合用药组HeLa细胞的凋亡率也显著高于紫杉醇组、rAd-P53单用组[(83±0.07)%vs(36±0.04)%、(62±0.05)%,P<0.05]。联合用药组HeLa细胞中VEGF的表达显著低于两单独用药组,HeLa细胞中VEGF表达分别下降(81±0.08)%、(45±0.07)%和(60±0.06)%(P<0.05)。结论:rAd-P53和紫杉醇联合用药抑制HeLa细胞的增殖、诱导细胞凋亡的效果优于单独用药,其机制可能与下调VEGF表达有关。Objective： To evaluate the effect of recombinant human adenovirus-P53 （rAd-P53） combined with paclita- xel on proliferation, apoptosis and vascular endothelial growth factor （VEGF） expression of cervical cancer HeLa cells. Methods： The effects of paclitaxel, rAd-P53 alone or in combination on the proliferation of HeLa cells were evaluated by MTY. The effects of paclitaxel, rAd-P53 alone or in combination on apoptosis of HeLa cells at 48 h were evaluated by DAPI stain. The effects of paclitaxel, tAd-P53 alone or in combination on VEGF expression in HeLa cells were examined by Western blotting. Results： Paclitaxel, rAd-P53 alone or in combination inhibited HeLa cell proliferation significantly at 24-72 h in dose-dependent and tlme-dependent manners. Furthermore, the inhibitory effect was more significant with rAd-P53 combined with paclitaxel than with paclitaxel or rAd-P53 alone group （ P 〈 0.05 ）. The coefficients of drug inter- action （CDI） of various doses of rAd-P53 combined with paclitaxel were less than 1, which indicated that there was a syn-ergism between them. At 48 h of treatment, rAd-P53 （5 x 107 VP/ml） combined with paclitaxel （3 Ixg/ml） showed stronger cell inhibition than the two drugs treated alone （ [54.0 ± 0.92] % vs [31.8 ± 0.58 ] %, [27.2 ±0.55 ] %, P 〈 0.05 ）. In addition, the combined group demonstrated more powerful ability in apoptosis induction than paelitaxel and rAd-P53 alone（ [ 83 ± 0.07 ] % vs [ 36± 0.04 ] %, [ 62 ± 0.05 ~ %, P 〈 0.05 ）, but the expression of VEGF in HeLa cells in the combined treatment group decreased more significantly than did the single drug groups （ [ 81 ± 0.08 ] % vs [45 ±0.07] %, [60 ±0. 061%, P 〈0.05）. Conclusion： rAd-P53 combined with paelitaxel shows more significant pro- liferation inhibition and apoptosis induction effects than does paelitaxel or rAd-P53 alone. Its mechanism may be associat- ed with down-regulation of VEGF expression.

关 键 词：重组人P53腺病毒 紫杉醇 宫颈癌 HELA细胞 VEGF 

分 类 号：R373.33[医药卫生—病原生物学] R730.54[医药卫生—基础医学]