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.
Li
Yi
Y
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.
Li
Long-Jiang
LJ
Zhang
Song-Tao
ST
Wang
Li-Juan
LJ
Zhang
Zhuang
Z
Gao
Ning
N
Zhang
Yuan-Yuan
YY
Chen
Qian-Ming
QM
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