Triptolide modulates tumour-colonisation and anti-tumour effect of attenuated Salmonella encoding DNase I
The strong human immunity and the associated toxicities of attenuated Salmonella severely limit the clinical use of Salmonella in tumour suppression. In the present study, we constructed an engineered VNP20009-DNase I strain and evaluated the synergistic effects of triptolide (TPL) and VNP20009-DNase I against melanoma in mice. Our results indicated that TPL could significantly inhibit the cell growth and cell migration and significantly enhanced the apoptosis rate of B16F10 cells in vitro. The in vivo results indicated that TPL markedly improved tumour colonisation of VNP20009-DNase I and led to a larger necrotic area in the melanoma. Moreover, the combination therapy significantly suppressed tumour volume and prolonged the life span of mice (P < 0.05) by upregulating the expression of Bcl-2/Bax and Caspase-3 and by downregulating the TLR4/NF-κB signalling, the expression of p-AKT/AKT and the production of proinflammatory factors. Therefore, the sound synergistic anti-tumour effects of TPL and VNP20009-DNase I indicate that the unconventional application of TPL and biological agents, approved by the China Food and Drug Administration (CFDA), can result in improved anti-cancer therapeutic outcomes.
KeywordsTriptolide VNP20009 DNase I Salmonella Cancer therapy
This work was supported by grants from the National Natural Science Foundation of China (No. 31560264, 81503364, 91639106, and 81873659), Excellent Youth Foundation of Jiangxi Scientific Committee (No. 20171BCB23028), the grant for Jiangxi Provincial Collaborative Innovation Center of Biopharmaceutics and Biotechnology (No. 2015202004), Key R & D plan of JiangXi Science and Technology Agency (No. 20181BBG70028), JiangXi Provincial Science and technology innovation team(20181BCB24003) and Science and technology plan of Jianxi Health Planning Committee (No. 20175526).
Compliance with ethical standards
Conflict of interest
All authors declare that they have no conflicts of interest.
All applicable international, national and/or institutional guidelines for the care and use of animals were followed.
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