A novel fusion suicide gene yeast CDglyTK plays a role in radio-gene therapy of nasopharyngeal carcinoma.

Abstract:

:To investigate a novel suicide gene for nasopharyngeal carcinoma (NPC) therapy, the yCDglyTK gene was constructed by fusing yeast cytosine deaminase (CD) and herpes simplex type 1 thymidine kinase. The expression of the yCDglyTK gene was detected by RT-PCR and Western blotting, and its bioactivity was demonstrated by an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay. An animal study was carried out in which BALB/C nude mice bearing yCDglyTK gene-modified tumors were treated with prodrugs and radiation. Our results revealed that the yCDglyTK gene could be expressed in CNE-2 cells in vitro. In MTT analysis, at the transfection rate of 10%, 66% cells were killed. The synergistic effect of CD and TK showed 91% of yCDglyTK-transfected cells were killed with the treatment of 5-fluorocytosine (5-FC) alone, 60% killed with ganciclovir (GCV) alone, and 75% killed with 5-FC and GCV together. In vivo, the tumor volume in all of the four prodrugs and/or radiation-treated groups were significantly different from that in the PBS-controlled group (P<.01); also yCDglyTK+prodrug+radiation group was different from the other three groups (P<.05). Our findings suggested there was a synergistic antitumor effect when combining suicide gene therapy and radiation, and yCDglyTK has potent antitumor efficacy and may be a candidate suicide gene for cancer therapy.

journal_name

Cancer Gene Ther

journal_title

Cancer gene therapy

authors

Xia K,Liang D,Tang A,Feng Y,Zhang J,Pan Q,Long Z,Dai H,Cai F,Wu L,Zhao S,Chen Z,Xia J

doi

10.1038/sj.cgt.7700728

subject

Has Abstract

pub_date

2004-12-01 00:00:00

pages

790-6

issue

12

eissn

0929-1903

issn

1476-5500

pii

7700728

journal_volume

11

pub_type

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