Co-culture with NK-92MI cells enhanced the anti-cancer
effect of bee venom on NSCLC cells by inactivation of NF-Κb
Arch Pharm Res, 2014 Jan 1
In the present study we experimented on a multimodal
therapeutic approach, such as combining chemotherapy agent (Bee venom) with
cellular (NK-92MI) immunotherapy. Previously bee venom has been found to show
anti-cancer effect in various cancer cell lines. In lung cancer cells bee venom
showed an IC50 value of 3 μg/ml in both cell lines. The co-culture of NK-92MI
cell lines with lung cancer cells also show a decrease in viability upto 50 %
at 48 h time point. Hence we used bee venom treated NK-92MI cells to co-culture
with NSCLC cells and found that there is a further decrease in cell viability
upto 70 and 75 % in A549 and NCI-H460 cell lines respectively.
We further investigated the expression of various apoptotic
and anti-apoptotic proteins and found that Bax, cleaved caspase-3 and -8 were
increasing where as Bcl-2 and cIAP-2 was decreasing. The expression of various
death receptor proteins like DR3, DR6 and Fas was also increasing.
Concomitantly the expression of various death receptor ligands (TNFalpha, Apo3L
and FasL) was also increasing of NK-92MI cells after co-culture. Further the
DNA binding activity and luciferase activity of NF-κB was also inhibited after
co-culture with bee venom treated NK-92MI cell lines. The knock down of death
receptors with si-RNA has reversed the decrease in cell viability and NF-κB
activity after co-culture with bee venom treated NK-92MI cells.
Thus this new approach can enhance the anti-cancer effect of
bee venom at a much lower concentration.
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