[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 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).


CONCLUSIONS
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.
Du
Chang-hu
CH
Guangzhou Institute of Respiratory Disease, Guangzhou Medical College, Guangzhou 510120, China.
Wu
Zhuang
Z
Xu
Jun
J
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000494:pharmacology* / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D008175:Lung Neoplasms / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011994:Recombinant Proteins; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000494:pharmacology* / Q000627:therapeutic use
D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin