Baculovirus Mediated Experimental Research on Targeted Egr1-Kringle 5 Gene Radiotherapy
in Lung Adenocarcinoma
404
baculoviruses provide a high transduction efficiency in
different cells and tissues, including several tumor cell
lines [21]. One of the attractive advantages of using
AcMNPV as a cancer gene therapy vector is the large
cloning capacity conferred by its 130-kb viral genome,
which may be used to deliver a large functional gene or
multiple genes from a single vector [22]. Other empirical
advantages of baculovirus vectors include easy construc-
tion of a recombinant viral vector and simple procedure
of purifying large quantities of viruses with high titers. It
would be possible to scale up the less labor-intensive
process to pharmaceutical levels [23]. A second problem
is the dose and the frequency of X-radiation to activate
Egr1 promoter and work as radiotherapy at the same time.
We found that the K5 expression activated by Egr1 pro-
moter dose-dependently increased in this vitro study, that
is, the most K5 expression was achieved using 10 Gy, the
highest dose in our study. Since a dose of 10 Gy is not
used in a curative treatment setting, and patients are not
treated with a single dose of irradiation but with fraction-
ated radiotherapy, we tried using continuously three-
times of X-radiation. To our surprise, the study demon-
strated that there’s no significant difference of K5 ex-
pression between high-dose groups and low-dose groups
after three times of irradiation. On the basis of these re-
sults we deduce this daily repeated small irradiation dose
results in the same activation efficiency of Egr1 promoter.
The mechanism has not been available yet. Moreover,
irradiated by 2 Gy daily is suitable for clinical treatment
and may decrease normal tissue toxicity compared with a
single large dose.
In summary, we report one therapeutic system with
radiation-inducible promoter, Egr1, which made it have
the capacity of temporal regulation as well as spatial re-
gulation. In this system, radiotherapy and gene therapy
worked simultaneously, and their effects were greater
than those of either modality alone. Low dose and more
times might be the most efficient therapeutic model of
this combined system. On the basis of the results above,
further study in vivo has been carried on to observe the
effect of this therapeutic system. And the potential bene-
fits of exogenous gene induction by radiotherapy include
increased local tumor control as well as the potential for
treatment of metastatic disease.
5. Acknowledgements
This work was supported by Shanghai Leading Aca-
demic Discipline Project S30203.
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