Effects of electrogenetherapy with p53wt combined with cisplatin on curvival of human tumor cell lines with different p53 status.
The aim of our study was to evaluate electrogenetherapy with p53wt alone or combined with cisplatin on two colorectal (HT-29 and LoVo) and two prostatic (PC-3 and Du145) carcinoma cell lines with different p53 status. In addition, the feasibility of electrogenetherapy with p53wt was tested also in vivo on PC-3 prostatic cancer xenografts. Electrogenetherapy with p53wt was dependent on the p53 status of the cell lines used. Electrogenetherapy was the most effective on the PC-3 (p53 null) and Du145 (p53mt) cells, and to the much lesser extent in LoVo cells (p53wt). The exception was the HT-29 cell line with overexpressed mutated p53, where electrogenetherapy with p53wt was the least effective. Sensitivity of the cell lines to cisplatin was independent of the p53 status. Furthermore, the presence of exogenous p53 due to electrogenetherapy did not enhance cisplatin cytotoxicity, since the combination of these therapies resulted in additive cytotoxic effect. The effectiveness of electrogenetherapy with p53wt was also demonstrated in vivo by successful treatment of subcutaneous PC-3 tumors in mice. In conclusion, our study shows that electrogenetherapy with p53wt is feasible, and resulted in comparable cytotoxic and antitumor effectiveness to viral-mediated p53wt gene therapy. This therapy was effective and dependent on the p53 status of the tumor cell lines. Combination of electrogenetherapy and cisplatin resulted in additional cell kill by cisplatin, and was not dependent on the p53 status.
Cemazar
Maja
M
Institute of Oncology, SI-1000 Ljubljana, Slovenia. mcemazar@onko-i.si
Grosel
Alenka
A
Glavac
Damjan
D
Kotnik
Vladimir
V
Skobrne
Mojca
M
Kranjc
Simona
S
Mir
Lluis M
LM
Andre
Frank
F
Opolon
Paule
P
Sersa
Gregor
G
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000628:therapy*; D003131:Combined Modality Therapy; D018274:Electroporation; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D006801:Humans; D008164:Luminescent Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000628:therapy*; D015996:Survival Rate; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000637:transplantation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D008164:Luminescent Proteins; D016159:Tumor Suppressor Protein p53; D049452:Green Fluorescent Proteins; D002945:Cisplatin