A comparison analysis of anti-tumor efficacy of adenoviral gene replacement therapy (p14ARF and p16INK4A) in human mesothelioma cells.
BACKGROUND
Tumor suppressor genes encode critical cell cycle regulatory proteins that are frequently mutated or deleted in cancer and, therefore, are important candidates for cancer treatment based on gene replacement strategies.


METHODS
We evaluated and compared the relative potential therapeutic efficacy of p14ARF and p16INK4A expressed in adenoviral vectors (Adp14ARF and Adp16INK4A, respectively) in three human mesothelioma cell lines.


RESULTS
The cytotoxic effects of expressed p16INK4A were significantly greater than that of p14ARF in both H28 and H2052 cells. Cell cycle G1 arrest occurred earlier with Adp16INK4A treatment than Adp14ARF (24 hours vs. 48 hours, respectively). Although both Adp14ARF and Adp16INK4A inhibited cell proliferation significantly and were potentiated by chemotherapy, Adp16INK4A appeared more potent.


CONCLUSIONS
Our results suggest that adenoviral gene-based therapy, especially using Adp16INK4A-based strategy, may be effective in the treatment of human mesothelioma.
Yang
Cheng-Ta
CT
Department of Internal Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.
You
Liang
L
Lin
Yu-Chin
YC
Lin
Chun-Liang
CL
Mccormick
Frank
F
Jablons
David M
DM
D000256:Adenoviridae / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology; D002453:Cell Cycle / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology; D003131:Combined Modality Therapy; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D008654:Mesothelioma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D017239:Paclitaxel / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D025803:Tumor Suppressor Protein p14ARF / Q000096:biosynthesis / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
D000970:Antineoplastic Agents; D019941:Cyclin-Dependent Kinase Inhibitor p16; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53; D017239:Paclitaxel; D002945:Cisplatin