摘要
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。
Objective To investigate the combination of wild-type p.53 （ wtp53 ） gene substitution and adriamycin （ADM） on the lung cancer in vivo. Methods The effect of combination of recombinant Adeno-wtp.53 （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-p.53 plus ADM chemotherapy）. The effect of rAd-p53 substitution and ADM on the drug sensitivity was evaluated. Results In vivo studies on nude mice model transplanted with NSCLC showed that, rAd-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 p.53 adenovirus with DNA-damaging drugs may increase the efficacy of chemotherapy in NSCLC and overcome primary drug resistance.
出处
《中华结核和呼吸杂志》
CAS
CSCD
北大核心
2006年第9期622-624,共3页
Chinese Journal of Tuberculosis and Respiratory Diseases
