The suppressed proliferation and premature senescence by ganciclovir in p53-mutated human non-small-lung cancer cells acquiring herpes simplex virus-thymidine kinase cDNA.
The concerted actions of molecular networks determine how cells undergo proliferation, death or aging. Here we show that the highly invasive, tumorigenic human non-small-cell-lung cancer (NSCLC) cells carrying mutated p53 alleles were transfected with herpes simplex virus-thymidine kinase (HSV-tk) cDNA and the selected clone was susceptible to exogenous ganciclovir (GCV). The work further indicated that, in the stable HSV-tk transfectants, GCV suppressed cell proliferation by inducing G(2)/M cell cycle arrest and premature senescence and the potency can be amplified through bystander effect. The growth suppression of the established tumor xenografts in nude mice can be successfully targeted by GCV. These data showed that the GCV-suppressed tumor cell proliferation can be coordinated by cell cycle arrest and cellular senescence in HSV-tk transfectant lacking wild-type p53.
Chiu
C-C
CC
Department of Biological Science, National Taiwan Normal University, Taipei, Taiwan, Republic of China.
Li
C-H
CH
Fuh
T-S
TS
Chen
W-L
WL
Huang
C-S
CS
Chen
L-J
LJ
Ung
W H
WH
Fang
K
K
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D018076:DNA, Complementary; D004305:Dose-Response Relationship, Drug; D005260:Female; D015774:Ganciclovir / Q000494:pharmacology*; D016158:Genes, p53; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D018139:Simplexvirus / Q000201:enzymology; D013937:Thymidine Kinase; D014162:Transfection; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000998:Antiviral Agents; D018076:DNA, Complementary; D013937:Thymidine Kinase; D015774:Ganciclovir