Anti-ANXA2 (aa 150-250) polyclonal antibody

The development of multidrug resistance greatly impedes effective cancer therapy. Recent advances in cancer research have demonstrated that acquisition of multidrug resistance by cancer cells is usually accompanied by enhanced cell invasiveness. Several lines of evidence indicated that cross activation of other signaling pathways during development of drug resistance may increase invasive potential of multidrug-resistant (MDR) cancer cells. However, the accurate mechanism of this process is largely undefined. In this study, to better understand the associated molecular pathways responsible for cancer progression induced by drug resistance, a MDR human breast cancer cell line SK-BR-3/EPR with P-glycoprotein overexpression was established using stepwise long-term exposure to increasing concentration of epirubicin. The SK-BR-3/EPR cell line exhibited decreased cell proliferative activity, but enhanced cell invasive capacity. We showed that the expression of metastasis-related matrix metalloproteinase (MMP)-2/9 was elevated in SK-BR-3/EPR cells. Moreover, SK-BR-3/EPR cells showed elevated activation of STAT3. Activation of STAT3 signaling is responsible for enhanced invasiveness of SK-BR-3/EPR cells through upregulation of MMP-2/9. STAT3 is a well-known oncogene and is frequently implicated in tumorigenesis and chemotherapeutic resistance. Our findings augment insight into the mechanism underlying the functional association between MDR and cancer invasiveness.

Objective Inactivity and inflammation are linked to obesity and insulin resistance. It was hypothesized that MyD88 (mediates inflammation) knockout from muscle (MusMyD88(-/-)) would prevent, whereas miR146a(-/-) (MyD88 inhibitor) would exacerbate, inactivity-induced metabolic disturbances. Methods Cre-control, MusMyD88(-/-), and miR146a(-/-) mice were given running wheels for 5 weeks to model an active phenotype. Afterward, half were placed into a small mouse cage (SMC) to restrict movement for 8 days. Body composition, muscle (H-3)2-deoxyglucose uptake, visceral fat histology, and tissue weight (hind limb muscles, visceral fat, and liver) were assessed. In skeletal muscle and visceral fat, RNA sequencing and mitochondrial function were performed on female MusMyD88(-/-) and Cre-control SMC mice. Results The SMC induced adiposity, hyperinsulinemia, and muscle insulin-stimulated glucose uptake, which was worsened in miR146a(-/-) mice. In females, MusMyD88(-/-) mice were protected. Female MusMyD88(-/-) mice during the SMC period (vs. Cre-control) exhibited higher Igf1 and decreased Ip6k3 and Trim63 muscle expression. Visceral fat transcript changes corresponded to improved lipid metabolism, decreased adipose expansion (Gulp1 up arrow, Anxa2 down arrow, Ehd1 down arrow) and meta-inflammation (Hmox1 down arrow), and increased beiging (Fgf10 up arrow). Ralgapa2, negative regulator of GLUT4 translocation, and inflammation-related gene 993011J21Rik2 were decreased in both muscle and fat. Conclusions Whole-body miR146a(-/-) exacerbated inactivity-induced fat gain and muscle insulin resistance, whereas MusMyD88(-/-) prevented insulin resistance in female mice.