重组腺病毒p53联用阿霉素对肺鳞癌移植瘤耐药性的影响

目的 探讨野生型p53基因联合阿霉素对肺癌化疗药物敏感性的影响及导入外源性野生型p53基因对肺癌原发性耐药的影响。方法 以携带野生型P53基因的复制缺陷型腺病毒（pAd-P53）感染荷瘤肺鳞癌裸鼠动物模型。分层随机法将鼠分为4组（每组6只）：单纯Ad-p53、单纯阿霉素（ADM）、Ad-p53加阿霉素组（联合组）及对照组，对照组注射同等剂量生理盐水。绘制肿瘤体积增长曲线，计算抑瘤率，观察肿瘤病理组织学变化。结果 联合组对裸鼠肿瘤重量增长抑制率为82．32％，对肿瘤体积增长抑制率为99．5％；而单独p53组对肿瘤重量增长抑制率／肿瘤体积增长抑制率分别为60．11％和85．4％；单独阿霉素组对肿瘤重量增长抑制率／肿瘤体积增长抑制率为35．4％和73．9％；对照组的肿瘤体积呈持续增长趋势。结论 野生型p53基因结合化疗药物对于提高抗肺癌药物的敏感性、克服原发耐药可能有一定的临床应用前景。

The combination of recombinant rAd-p53 and adriamycin for management of primary drug resistance in chemotherapy of lung squamous cell cancer

Objective To investigate the combination of wild-type p53(wtp53)gene substitution and adriamycin(ADM)on the lung cancer in vivo.Methods The effect of combination of recombinant Adeno-wtp53(rAd-p53)and ADM on reversing primary drug resistance to ADM was studied for the non- small cell lung cancer(NSCLC)in a nude mice model developed by subcutaneously transplanting with the 16HBE lung cancer cell line.Twenty four nude mice with loaded tumors were randomly divided into 4 groups (no treatment,rAd-p53 treatment alone,ADM treatment alone,combination of rAd-p53 plus ADM chemotherapy).The effect of tAd-p53 substitution and ADM on the drug sensitivity was evaluated.Results In vivo studies on nude mice model transplanted with NSCLC showed that,tAd-p53 treatment alone suppressed tumor growth by 60.11% of the tumor weight and 85.4% by the volume(n=6),while the combination of rAd-p53 with ADM suppressed tumor growth more significantly(82.32%,99.5%, respectively,n=6).The treatment with Adriamycin alone was less effective(35.4%,73.9%, respectively,n=6).Conclusion Combination of rAd-p53 and ADM significantly increased the sensitivity of NSCLC tumor graft to ADM,suggesting that the combination of replication-deficient wild p53 adenovirus with DNA-damaging drugs may increase the efficacy of chemotherapy in NSCLC and overcome primary drug resistance.