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Apoptosis serves a pivotal role in the pathogenesis of osteoarthritis (OA). Increasing evidence has demonstrated that paeoniflorin exerts key properties (including anticancer, anti-inflammation and neuroprotective) for clinical applications. However, the precise role of paeoniflorin in articular cartilage apoptosis remains unknown. The present study explored the effects and potential molecular mechanism of paeoniflorin on rat chondrocyte apoptosis. Rat articular chondrocytes were cultured in monolayers. The lactate dehydrogenase (LDH) release rate of cells was determined by an LDH release assay. Annexin V-fluorescein isothiocyanate and propidium iodide staining were performed to detect early and advanced apoptotic cells by flow cytometry. The activity of caspase-3 in chondrocytes was determined using a caspase-3 activity assay. The expression of B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) was examined by reverse transcription‑quantitative polymerase chain and western blotting. The present study also examined the protein kinase B (Akt) signaling pathway by western blotting. Treatment with 25 or 50 µM paeoniflorin markedly decreased the release of LDH and the ratio of apoptotic cells in interleukin (IL)-1β-induced rat chondrocytes. Paeoniflorin treatment decreased the mRNA and protein levels of Bax, and increased the level of Bcl-2. Paeoniflorin also reduced the activity of caspase-3 in chondrocytes. Furthermore, paeoniflorin was determined to regulate the Akt signaling pathway by increasing Akt phosphorylation. Therefore, paeoniflorin may exert its protective effect by inhibiting apoptosis in IL-1β-induced rat chondrocytes and thus, may be an effective agent in the prevention and treatment of OA. [ABSTRACT FROM AUTHOR]

The treatment of renal cell carcinoma (RCC) with chemotherapy remains a challenge; therefore, improving the knowledge of the molecular mechanisms underlying RCC chemoresistance and developing novel therapeutic strategies is important. Dedicator of cytokinesis 1 (DOCK1), the first member of the DOCK family to be discovered, displays various roles during tumorigenesis; however, its role during RCC progression is not completely understood. Therefore, the present study aimed to clarify the function of DOCK1 and 1-[2-(3′-(trifluoromethyl)-(1,1′-biphenyl)-4-yl)-2-oxoethyl]-5-pyrrolidinylsulfonyl-2 (1H)-pyridone (TBOPP), a DOCK1-sensitive inhibitor, during RCC development and chemoresistance. The results of CCK-8 and EdU assay indicated that TBOPP decreased RCC cell viability and proliferation compared with the control group, and sensitized RCC cells to cisplatin. Moreover, RCC cells with high DOCK1 expression levels displayed increased resistance to cisplatin, whereas DOCK1 knockdown enhanced the lethal effects of cisplatin on RCC cells. Furthermore, the results determined by western blotting, CCK-8 and cell apoptosis assay indicated that TBOPP effectively reduced DOCK1 expression levels compared with the control group, and the TBOPP-mediated cisplatin sensitizing effect was mediated by DOCK1 inhibition. The present study suggests that DOCK1 plays a vital role in RCC cell chemoresistance to cisplatin; therefore, TBOPP may serve as a novel therapeutic agent for RCC chemoresistance. [ABSTRACT FROM AUTHOR]

The aim of the current study was to investigate the expression and role of microRNA-486-5p (miR-486-5p) in hypertrophic scar (HS) formation, and to examine the associated mechanisms. First, miR-486-5p expression was detected in HS tissues and human hypertrophic scar fibroblasts (hHSFs) by reverse transcription-quantitative polymerase chain reaction. Target genes of miR-486-5p were predicted using TargetScan and verified by dual-luciferase reporter assays. To investigate the role of miR-486-5p in HS formation, miR-486-5p was overexpressed in hHSFs through transfection with miR-486-5p mimics. MTT, cell apoptosis and cell cycle assays were preformed to investigate the proliferation, cell apoptosis and cell cycle distribution of hHSFs, respectively. Additionally, protein expression was measured by western blot analysis. The results demonstrated that miR-486-5p expression was significantly decreased in HS tissues and cells. Mothers against decapentaplegic homolog (Smad)2 was a target gene of miR-486-5p, and it was negatively regulated by miR-486-5p. It was also found that Smad2 expression was significantly increased in HS tissues and cells. Further analysis indicated that miR-486-5p mimic transfection inhibited the proliferation, induced cell apoptosis and increased G1/S phase arrest in hHSFs. Furthermore, the expression of cyclin-dependent kinase (CDK)2, CDK4 and apoptosis regulator Bcl-2 was repressed, while apoptosis regulator BAX expression was enhanced by miR-486-5p mimic transfection. Notably, the effects of miR-486-5p mimic on hHSFs were significantly eliminated by Smad2 plasmid transfection. Taken together, these results demonstrated that miR-486-5p inhibited the proliferation, induced apoptosis and increased G1/S phase arrest of hHSFs by targeting Smad2. miR-486-5p may be a promising therapeutic target for HS management. [ABSTRACT FROM AUTHOR]

Aspirin as an antitumor drug has been studied in various malignancies with regards to its effects on apoptosis, proliferation, metastasis and senescence of tumor cells. However, the clinical application is limited by its side effects. Nutlin‑3 is a novel antitumor compound, which has not been clinically approved. The present study investigated the value of combining aspirin and nutlin‑3 on hepatocellular carcinoma (HCC) cells. MTT was performed to detect the proliferation of HepG2 cells treated with aspirin or/and nutlin‑3. Transwell invasion assays were performed to estimate the invasion ability of HepG2 cells treated with aspirin or/and nutlin‑3. Then the apoptotic analysis of HepG2 cells evaluated the synergistic effect of aspirin and nutlin‑3. Apoptosis markers, including B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax), caspase‑3, caspase‑8 and caspase‑9 were estimated by western blot analysis at various time points. In addition, a Xenograft mouse model was established by infection with HepG2 cells, and aspirin and/or nutlin‑3 was administrated to verify the anti‑apoptotic effect of the two drugs in vivo. A high dose of aspirin and nutlin‑3 inhibit the proliferation and apoptosis of HepG2 cells. The antitumor effect was enhanced with the combined treatment of the two drugs, particularly in the group with a low concentration of aspirin and nutlin‑3. Nutlin‑3 was able to increase the level of Bax in HepG2 cells treated with aspirin significantly after treatment for 8 h. When treated with a low concentration of aspirin and nutlin‑3, the level of Bax in HepG2 cells was enhanced for 2 h. In the animal model, tumor volume and tumor angiogenesis were significantly decreased in combination group compared with other groups (P<0.01). Although there were side effects in the group treated with aspirin alone, no side effects were observed in the combination group. Nutlin‑3 enhanced the apoptotic effect of a low dose of aspirin by upregulating Bax expression in the HepG2 cell line and in vivo. The synergistic effect of nutlin‑3 in aspirin antitumor therapy contributed to diminishing the dose of aspirin required and decreased the occurrence of adverse drug events in HCC through targeting the Bcl‑2/Bax signaling pathway. [ABSTRACT FROM AUTHOR]