Retraction Note: Combination therapy with metformin and IL-12 to inhibit the growth of hepatic carcinoma by promoting apoptosis and autophagy in HepG2-bearing mice.

The article "Combination therapy with metformin and IL-12 to inhibit the growth of hepatic carcinoma by promoting apoptosis and autophagy in HepG2-bearing mice, by Z. Jin, B.-X. Jia, L.-D. Tan, Q.-M. Chen, Y.-H. Liu, published in Eur Rev Med Pharmacol Sci 2020; 24 (23): 12368-12379-DOI: 10.26355/eurrev_202012_24031-PMID: 33336757" has been retracted by the authors as they cannot ensure the reliability of the manuscript due to inaccuracies in the conclusions and in the experiment (the cell migration and invasion assay along with the cell cycle arrest assay are missing). The Publisher apologizes for any inconvenience this may cause https://www.europeanreview.org/article/24031.

Combination therapy with metformin and IL-12 to inhibit the growth of hepatic carcinoma by promoting apoptosis and autophagy in HepG2-bearing mice.

OBJECTIVE: To investigate the effects and mechanism of metformin (Met) combined the interleukin-12 (IL-12) on inhibiting hepatoma HepG2 cell proliferation via in vitro and in vivo assays. MATERIALS AND METHODS: MTT assay was used to detect inhibitory effects of Met, IL-12 alone or combination on HepG2 cells proliferation. Half inhibitory concentration (IC50) and combination index (CI) were also calculated. Anti-tumor effects of combination or monotherapy on the HepG2-bearing mice were investigated and protein expression levels of apoptosis, as well as the Akt/mTOR/STAT3 signaling pathway-related factors were detected by Western blot. RESULTS: MTT results showed that the inhibitory effect of Met combined with IL-12 on HepG2 cell proliferation was significantly enhanced (both p<0.01) compared with monomer therapy group with a significant synergistic effect (CI<1). The apoptosis rate of HepG2 cells treated with Met combined with IL-12 were 88.12±7.15% and significantly higher than the others (all p<0.01). Moreover, combination treatment significantly suppressed hepatoma growth and increased the survival rate of HepG2-bearing mice without evident body weight loss. Western blot analysis showed that Met combined with IL-12 significantly increased the expression of autophagy-related marker proteins, downregulated the protein expression levels of Bcl-2, p-Akt, p-mTOR, p-STAT3, upregulated the expression level of BAX in both HepG2 cells and tumor tissues. CONCLUSIONS: Met combined with IL-12 exhibited a synergistic antitumor effect on hepatoma HepG2 cells, and the mechanism may be related to its common inhibition of Akt/mTOR/STAT3 signaling pathway and increase of autophagy in HepG2-bearing mice.

Metabolomic profiling reveals similar cytotoxic effects and protective functions of quercetin during deoxynivalenol- and 15-acetyl deoxynivalenol-induced cell apoptosis.

Among the family of mycotoxins of deoxynivalenol (DON) detected in nature, high proportions of 15-acetyldeoxynivalenol (15ADON) co-occur with the prototype DON and increase the combined exposure and synergistic health risks. The current study aimed to explore the mechanisms underlying the toxicity of 15ADON and compare them with those of DON. As the natural flavonoid compound quercetin (QUE) possesses antioxidant properties, we also aimed to determine the antioxidant effects of QUE on the tested mycotoxins. First, the global metabolomics approach was applied and showed that the metabolites produced from 15ADON or DON were almost identical, while QUE reversed the changes in the levels of key metabolites. Specifically, both DON and 15ADON activated the cell apoptosis pathway mediated by p38 and JNK, but inhibited the cell survival pathway mediated by ERK1/2 in GES-1 cells. Simultaneously, 15ADON induced FOXO3a nuclear translocation, similar to the results described for DON in our recent report. Furthermore, the addition of QUE appeared to counteract the detrimental effects of 15ADON and DON. We observed the effects of QUE treatment on mutant yeast strains with defects in their antioxidant system. More interestingly, QUE also substantially restored the increased ROS levels and the inhibited the growth rate following exposure to the mycotoxins DON and 15ADON. The data reported here support the hypothesis that QUE rescues the toxic effects of DON or 15ADON due to the similar mechanisms of DON and 15ADON toxicity.