IRE1α endonuclease is a key regulator of endoplasmic reticulum (ER) stress that controls cell survival/apoptosis in cancers. Inhibition of IRE1α endonuclease leads to decreased splice XBP1 which decreases cell proliferation and increases cell death in cancer cells. Therefore, this study investigated the effects and mechanism of STF‐083010 (an IRE1α inhibitor) on the cell growth/apoptosis of ovarian malignant cells via the XBP1‐CHOP‐Bim pathway following the induction of ER stress (ERS). ERS in OVCAR3 and SKOV3 cells was measured using Thioflavin T staining. The expression of ER stress response genes was evaluated by QRT‐PCR. The levels of XBP1(s), PERK, phospho‐PERK, p‐PP2A, ATF4, BIP/GRP78, CHOP, and Bim proteins were evaluated using western blotting. Cell viability and apoptosis in STF‐083010 and Tunicamycin (Tm) co‐treated cells were assessed using BrdU, MTT, Annexin V‐FITC/PI staining, and caspases‐12 and ‐3 activity assays. The results showed increased XBP1, CHOP, and ATF‐4 mRNA expression levels as well as high protein aggregation in STF‐083010 and Tm co‐treated cells. The IRE1α inhibitor down‐regulated sXBP1 and BIP proteins, while XBP‐1, p‐PERK, ATF‐4, CHOP, and Bim proteins were up‐regulated. STF‐083010 reduced cell proliferation and induced apoptosis through the activation of caspases‐12 and ‐3 and Bax/Bcl‐2 protein expression. In summary, the present data revealed the effects of STF‐083010 in ER stress and apoptosis as well as signaling via XBP1/CHOP/Bim mediators. Thus, STF‐083010 is proposed as a new target for the control of ERS in ovarian cancer cells.

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Background Meteorin-like (Metrnl) is an adipokine with insulin sensitizing and anti-inflammatory properties that has been discovered recently. The relation among Metrnl, Inflammatory Bowel Disease (IBD), and obesity has been unexplored yet. Methods The present study was conducted on 54 healthy control, 42 Ulcerative Colitis (UC), and 43 Crohn’s disease (CD) patients who were diagnosed by pathological examination. In all participants, serum levels of adiponectin, Metrnl, interleukin (IL)-6, and Tumor necrosis factor (TNF-α) were measured using ELISA kits. Results Metrnl concentration was considerably lower in both UC (85.25 ± 36.55 pg/mL) and CD (76.93 ± 27.92 pg/mL) patients in comparison to control (107.52 ± 35.33 pg/mL). In addition, it was seen that both patient groups have a decreased level of adiponectin compared to the controls. Besides that, the level of IL-6 and TNF-α were significantly greater in the patient groups. Moreover, the result showed that the level of Metrnl is inversely correlated with body mass index (BMI) in the controls and the patients. Metrnl levels are also inversely associated with IL-6, and TNF-α in both of the patient groups. Conclusions The current study is the first one reporting the decreased levels of Metrnl in serum among patients with IBD, which is inversely related with BMI, TNF-α, and IL-6. These results suggested a possible relation of Metrnl with the pathogenesis of IBD, particularly through inflammatory process, although further studies are warranted to dissect the possible mechanism.

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