In vitro and clinical studies of gene therapy with recombinant human adenovirus-p53 injection for oral leukoplakia.
OBJECTIVE
Oral leukoplakia is a well-recognized precancerous lesion of squamous cell carcinoma. When accompanied with abnormal p53 expression, it suffered a higher risk of canceration. The present study was carried out to test whether the recombinant human adenovirus-p53 could introduce wild-type p53 gene to oral leukoplakia cells and induce cell cycle arrest and apoptosis.


METHODS
We select p53(-) oral dysplastic keratinocyte POE-9n, to observe the growth inhibition, cell cycle change, apoptosis-induced effects, and elaborate the corresponding molecular mechanism of recombinant adenovirus-p53 on POE-9n cells. Meanwhile, we evaluate the feasibility, safety, and biological activity of multipoints intraepithelial injections of recombinant adenovirus-p53 in 22 patients with dysplastic oral leukoplakia.


RESULTS
Exogenous p53 could be successfully transduced into POE-9n cells by recombinant adenovirus-p53. The optimal infecting titer in this study was multiplicity of infection (MOI) = 100. Recombinant adenovirus-p53 could strongly inhibit cell proliferation, induce apoptosis, and arrest cell cycle in stage G(1) in POE-9n cells by inducing p21(CIP/WAF) and downregulating bcl-2 expression. In the posttreatment patients, p53 protein and p21(CIP/WAF) protein expression were significantly enhanced, yet bcl-2 protein presented low expression. Sixteen patients showed clinical response to the treatment, and 14 patients showed obvious histopathologic improvement.


CONCLUSIONS
Intraepithelial injections of recombinant human adenovirus-p53 were safe, feasible, and biologically active for patients with dysplastic oral leukoplakia.
State Key Laboratory of Oral Diseases, Department of Head and Neck Oncology, West China College of Stomatology, and West China Health Hospital, Sichuan University, Chengdu, PR China.
Yi
Y
Li
Long-Jiang
LJ
Li
Song-Tao
ST
Zhang
Li-Juan
LJ
Wang
Zhuang
Z
Zhang
Ning
N
Gao
Yuan-Yuan
YY
Zhang
Qian-Ming
QM
Chen
D000260:Adenoviruses, Human / Q000235:genetics*; D002460:Cell Line; D004274:DNA, Recombinant; D005240:Feasibility Studies; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D007972:Leukoplakia, Oral / Q000628:therapy*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D004274:DNA, Recombinant; D016159:Tumor Suppressor Protein p53