Folic Acid-Modified Liposome Quercetin Induces Apoptosis of Triple-Negative Breast Cancer Cells via Mitochondrial Apoptosis Mediated by JAK2/STAT3 Signaling Pathway / 肿瘤防治研究

Objective To investigate the effect of folic acid–modified liposome quercetin (FLQ) on the proliferation and apoptosis of triple negative breast cancer (TNBC) cells and explore its underlying mechanism. Methods CCK-8 was used to detect the effect of FLQ on TNBC cell viability. Colony formation assay was conducted to detect the effect of FLQ on TNBC cell proliferation. Flow cytometry was performed to detect the effect of FLQ on TNBC cell apoptosis, the levels of intracellular ROS, and mitochondrial membrane potential. Western blot analysis was conducted to detect the expression levels of JAK2/STAT3 signaling pathway-related and apoptosis-related proteins. Results FLQ inhibited the proliferation and promoted the apoptosis of MDA-MB-231 cells (P=0.023, P<0.001). It promoted mitochondrial membrane potential collapse and increased the intracellular ROS levels of MDA-MB-231 cells (P=0.003, P=0.034); inhibited the phosphorylation levels of JAK2 and STAT3; upregulated the expression levels of the proapoptotic proteins Bax, Bak, cytochrome C, and Cleaved-Caspase-3 (P<0.001, P<0.001); and downregulated the expression levels of the antiapoptotic proteins Bcl2 and Bcl-xL (P=0.037, 0.028). Conclusion FLQ inhibits the proliferation and induces the apoptosis of MDA-MB-231 cells. These effects may be related to the activation of the mitochondrial apoptosis pathway through the inhibition of the JAK2/STAT3 signaling pathway.

Bioinformatic analysis of the polymorphism and function of IGF2R gene 3′untranslated region / 医学研究生学报

Objective Genetic variants in microRNA (miRNA) binding regions of the gene 3′untranslated region (3′UTR) can affect the regulation of gene expression .The aim of this study was to predict insulin like growth factor 2 receptor (IGF2R) 3′UTR variants and to test their effects on IGF2R gene expression by bioinformatic analysis . Methods Single nucleotide polymorphisms (SNPs) with minor allele frequency (MAF) in the IGF2R gene 3′UTR were obtained from online databases .The frequency distribution of all the selected IGF2R 3′UTR variants genotypes among the different populations and the linkage disequilibrium ( LD) values of all SNPs were calculated .Additionally , the potential miRNA binding sites were also predicted with the help of online bioinformatic tool . Finally, correlation analysis of the mRNA expression of IGF 2R genotype and different variant genotypes in the lymphoblastoid cell lines was performed. Results In total, 33 SNPs were reported in the 3′UTR, of which only five SNPs (rs8191959, rs200237825, rs3832385, rs201568808, rs1050015) had available minor allele frequency (MAF) values ( >0.05).And only the effect of rs1050015 variant on IGF2R mRNA expression level had significant difference (P=0.010). Conclusion The expression of IGF2R gene can be up-regulated by rs10500105 variant in the 3′UTR, which might support its use as markers of cancer risk and individualized treatment.