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Dysregulated crosstalk between different signaling pathways contributes to tumor development, including resistance to cancer therapy. In the present study, we found that the mitogen-activated extracellular signal-regulated kinase (MEK) inhibitor trametinib failed to suppress the proliferation of PANC-1 and MGC803 cells by activating the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway, while the JAK2 inhibitor fedratinib failed to inhibit the growth of the PANC-1 cells upon stimulation of extracellular signal-regulated kinase (ERK) signaling. In particular, the most prominent enhancement of the anti-proliferative effect resulted from the concurrent blockage of the JAK2/STAT3 and ERK signaling pathways. Furthermore, the combination of the two inhibitors resulted in a reduced tumor burden in mice. Our evidence suggests novel crosstalk between JAK2/STAT3 and ERK signaling in gastric cancer (GC) and pancreatic ductal adenocarcinoma (PDAC) cells and provides a therapeutic strategy to overcome potential resistance in gastrointestinal cancer.

Objective To investigate the synergistic effects of cryptotanshinone (CPT) and doxorubicin (DOXO) on induction of apoptosis in human gastric cancer cells and the mechanisms.Methods Cell proliferation and apoptosis were detected using the CCK8 assay and AnnexinV/PI staining, respectively. Western blotting was used to determine the levels and phosphorylation of proteins encoded by STAT3-regulated genes and the cleaved forms of caspases and PARP.Results CPT significantly potentiated the antiproliferative effect of DOXO in gastric cancer cell lines. CPT combined with DOXO induced apoptosis and cleavage of caspases-3,-7,-9 as well as PARP. CPT or a STAT3 siRNA significantly suppressed constitutive and IL-6-induced phosphorylation of STAT3 Tyr705, decreasing the levels of proteins encoded by STAT3-target genes (Bcl-xL, Mcl-1, survivin, and XIAP).Conclusions CPT enhanced the anticancer activity of DOXO in gastric cancer cells via STAT3 inactivation and suppression STAT3-regulated antiapoptotic gene expression, indicating that DOXO combined with CPT may serve as effective therapy for gastric cancer.

One of the main target organs for the lanthanides (Ln) is bone. Previous studies revealed that ytterbium (Yb) produced damage to the skeletal system in vivo. But the effects of Yb3+on bone marrow stromal cells (BMSCs) in vitrohad not been reported. In this paper, cell viability, apoptosis, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) and lactate dehydrogenase (LDH) were measured in order to study the effects of Yb3+on BMSCs. The results indicated that Yb3+displayed a slight positive effect on the BMSCs viability at concentrations of 1×10−6, 1×10−5, and 1×10−4mol/L, but turned to decrease the viability of BMSCs at the highest concentration of 1×10−3mol/L for 24, 48 and 72 h. Yb3+at 1×10−3mol/L promoted apoptosis of BMSCs, increased the levels of ROS and LDH, and decreased MMP in BMSCs. It suggested that the precipitate of YbPO4might decrease the viability of BMSCs. Yb3+induced the apoptosis of BMSCs via mitochondrial pathway. The results might be useful for more rational application of Yb-based compounds in the future.

Alpha linolenic acid (ALA) is an essential polyunsaturated fatty acids that can improve human health. Rapeseed is the second largest oil crop in the world but the ALA content in its seed fatty acids is only about 10%. Two rapeseed germplasms YH25005 and R8Q10 with high content (up to 21%) ALA were developed by intervarietal crossing. They were used as the maternal parent (P1) when crossed with a low ALA parent SW (P2) to produce the seeds of the F1hybrid, F2, and backcrosses to P1(BCP1) and P2(BCP2). A multigeneration joint segregation analysis was conducted to determine major gene + polygene effects of the content of three major unsaturated fatty acids including oleic (OA), linoleic (LA) and ALA. The results showed that, although some genes favorable to ALA accumulation were not allelic in R8Q10 and YH25005, all the inheritances of OA, LA and ALA in YH25005×SW and R8Q10×SW followed a genetic model of ‘two pairs of additive major genes + additive-dominant polygenes’. It is suggested that the contents of OA, LA and ALA are closely related and the major genes in the parent SW containing loss-of- function mutations in FAD2and FAD3loci had strong effect to reduce ALA and elevate OA. However, total genetic effect of the polygenes was greater than that of the two major genes, especial on ALA content. It indicated that it is necessary to employ a larger F2population to find the plant that accumulate enough minor-effect polygenes for high ALA content. The results are useful for high ALA rapeseed breeding and future work of gene mapping.