Objective To explore the role of forkhead box protein O3a (FOXO3a) in inhibiting the proliferation and metastasis of breast cancer cells by downregulation of vascular endothelial growth factorA (VEGF-A).Methods Cell proliferation bioassay and plate clone formation assay were used to compare the changes of proliferation after siRNA interference.Wound healing and Transwell were used to compare the changes of invasion metastasis after interference.Meanwhile,the changes of VEGF-A expression in the cells before and after interference were compared by real time polymerase chain reaction (RT-PCR) and Western blot.Furthermore,the expressions of mRNA FOXO3a and VEGF-A were detected in 20 cases of breast cancer patients in breast cancer tissues and adjacent normal breast tissues.Results The MCF-7 and MDA-MB-231 cells were increased in cell proliferation and invasion after interference.Further studies found that mRNA and protein expression of VEGF-A were up-regulated in MCF-7 and MDA-MB-231cells after interference.In vivo the expression of FOXO3a was lower in 15 cases of cancer compared to normal tissues,and the expression of VEGF-A was high in 15 cases of cancer (75％).FOXO3a and VEGF-A expression was highly negatively correlated.Conclusions This study showed that FOXO3a could inhibit the proliferation and invasion of breast cancer cells,which might be regulated by VEGF-A.It provides an important theoretical evidence for targeted inhibition of breast cancer metastasis.

Aristolochic acids (AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I (AAI) reacts with DNA to form covalent aristolactam (AL)-DNA adducts, leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in mainland China. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood.