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（3 μg/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 paclitaxel 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 MTT. 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, rAd-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 time-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 interaction (CDI) of various doses of rAd-P53 combined with paclitaxel were less than 1, which indicated that there was a synergism between them. At 48 h of treatment, rAd-P53 (5×107 VP/ml) combined with paclitaxel (3 μg/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 paclitaxel 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 \[45±0.07\]%, \[60±0.06\]%, P<0.05). Conclusion: rAd-P53 combined with paclitaxel shows more significant proliferation inhibition and apoptosis induction effects than does paclitaxel or rAd-P53 alone. Its mechanism may be associated with down-regulation of VEGF expression.

江苏省卫生厅康莱特临床肿瘤研究基金资助项目（No.P200943）