Adenovirus KH901 promotes 5-FU antitumor efficacy and S phase in LoVo cells.
A combination of oncolytic and chemotherapeutic agents has been used to kill cancer cells. However, the effect of oncolytic adenoviruses on the cell cycle remains to be determined. Cytotoxicity assays were performed to determine cell death in cells treated with 5-fluorouracil (5-FU) alone or in combination with the oncolytic adenovirus KH901. Dynamic changes in the cell cycle, cell proliferation, and apoptosis-related proteins including p-AKT, Bcl-2, Bax, and caspase 3 were investigated after treatment with 5-FU with or without KH901. A higher proportion of S-phase cells were observed after treatment with KH901 and 5-FU than with 5-FU alone. p-AKT, Bcl-2, and Bax expression was increased upon treatment with KH901, whereas the expression of caspase-3 was not induced upon treatment with KH901 with or without 5-FU. KH901 exhibited significant potential as an oncolytic adenovirus and increased cell death in combination with 5-FU in LoVo cells, as compared to 5-FU alone. In conclusion, KH901 stimulates LoVo cells to enter the S-phase by activation of p-AKT, which could partly explain its synergistic effect with 5-FU on LoVo cell cytotoxicity.
Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Wei
W
Peng
Jin
J
Li
X G
XG
Yin
J F
JF
Xu
L Z
LZ
Cheng
D000256:Adenoviridae / Q000502:physiology*; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology; D003588:Cytopathogenic Effect, Viral; D005434:Flow Cytometry; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D009369:Neoplasms; D016196:S Phase / Q000187:drug effects*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000964:Antimetabolites, Antineoplastic; D051028:bcl-2-Associated X Protein; D005472:Fluorouracil