PUMA基因对耐药绒癌化疗敏感性的影响

Effect of PUMA on sensitivity of drug resistant choriocarcinoma cells to chemotherapeutic agents

目的研究p53上调凋亡调控因子(PUMA)对绒癌耐药细胞jeg-3/vp16化疗敏感性的影响。方法PUMA在化疗药物加入前用PUMA感染jeg-3/vp16细胞,观察抑制增殖的效应并探讨其机制。结果Ad-PUMA体内体外均显著增加耐药细胞对化疗药物的敏感性,增加化疗药物诱导绒癌细胞凋亡的能力。jeg-3/vp16的PUMA表达降低,而且对5-氟尿嘧啶(5-Fu)和依托泊苷(vp16)反应减弱。结论PUMA在化疗药物诱导凋亡的过程中发挥作用,Ad-PUMA与化疗药物合用后显著增加耐药绒癌细胞对化疗药物的敏感性。

Objective. To investigate the effect of PUMA on the sensitivity of drug-resistant choriocarcinoma cells to anticancer drugs. Methods： PUMA, carried by adenovirus （Ad-PUMA）, was added into the culture medium of a drugresistant choriocarcinoma cell line jeg-3/vp16, before the chemotherapeutic agents 5-Fu, Vpl6 or MTX added. The effects and the mechanism of PUMA in vitro and in vivo were examined. Results. The cell proliferation was inhibited significantly when treated with combination of Ad-PUMA and the anticancer drugs, when compared to that treated with gnticancer drugs alone in vitro as well as in vivo. The apoptosis rate of the choriocarcinoma cells increased significantly when 5-Fu or Vp16 was combined with Ad-PUMA, observed from sub-G1 measurement and DAPI staining. PUMA was expressed lower in jeg-3/vp16 than in jeg-3, jeg-3/vpl6 responded much less sensitively to 5-Fu and vpl6 treatment than jeg-3, though PUMA was up-regulated in both cells. Conclusions. PUMA is a crucial factor in the apoptosis induced by anticancer drugs. Low dose of Ad- PUMA significantly restored the sensitivity of choriocarcinoma cells to chemotherapeutic agents in vitro and in vivo.