[Wnt5a modulates vincristine resistance through PI3K/Akt/GSK3ß signaling pathway in human ovarian carcinoma SKOV3/VCR cells].

The aim of this study was to investigate the effect of Wnt5a on the vincristine (VCR) resistance in human ovarian carcinoma SKOV3 cells and its possible mechanism. The drug-resistant SKOV3/VCR cells were established by stepwise exposure to VCR, and then the SKOV3/VCR cells were stably transfected with specific shRNA interference plasmid vector targeting for Wnt5a. The mRNA expression level of Wnt5a was measured by RT-PCR. CCK-8 assay was used to detect the cell viability of SKOV3/VCR cells. The apoptosis was analyzed by flow cytometry. The protein expression levels of Wnt5a, MDR1, Survivin, ß-catenin, Akt, p-Akt(S473), GSK3ß and p-GSK3ß(Ser9) were detected by Western blot. The result showed that SKOV3/VCR cells had significantly higher protein expression levels of Wnt5a, MDR1, Survivin and ß-catenin, phosphorylation levels of Akt and GSK3ß, and mRNA expression level of Wnt5a, compared with SKOV3 cells (P < 0.05). WNT5A gene silencing significantly increased the sensitivity of SKOV3/VCR cells to VCR, the IC50 of VCR being decreased from 38.412 to 9.283 mg/L (P < 0.05), synergistically enhanced VCR-induced apoptosis of SKOV3/VCR cells (P < 0.05), down-regulated the protein expression levels of MDR1, ß-catenin and Survivin (P < 0.05), and inhibited phosphorylation of Akt and GSK3ß (P < 0.05). Meanwhile, LY294002 (PI3K inhibitor) decreased the protein expression levels of MDR1, ß-catenin and Survivin, as well as the phosphorylation levels of Akt and GSK3ß in SKOV3/VCR cells (P < 0.05). These results suggest that WNT5A gene silencing reverses VCR resistance in SKOV3/VCR cells possibly through blocking the PI3K/Akt/GSK3ß/ß-catenin signaling pathway, and thus down-regulating the protein expression levels of MDR1 and Survivin.

Multiorgan dysfunction syndrome due to high-dose cantharidin poisoning: A case report.

BACKGROUND: This report delves into the diagnostic and therapeutic journey undertaken by a patient with high-dose cantharidin poisoning and multiorgan dysfunction syndrome (MODS). Particular emphasis is placed on the comprehensive elucidation of the clinical manifestations of high-dose cantharidin poisoning, the intricate path to diagnosis, and the exploration of potential underlying mechanisms. CASE SUMMARY: A patient taking 10 g of cantharidin powder orally subsequently developed MODS. The patient was treated with supportive care, fluid hydration and antibiotics, and hemoperfusion and hemofiltration therapy for 24 h and successfully recovered 8 d after hospital admission. Cantharidin poisoning can cause life-threatening MODS and is rare clinically. This case underscores the challenge in diagnosis and highlights the need for early clinical differentiation to facilitate accurate assessment and prompt intervention. CONCLUSION: This article has reported and analyzed the clinical data, diagnosis, treatment, and prognosis of a case of high-dose cantharidin poisoning resulting in MODS and reviewed the relevant literature to improve the clinical understanding of this rare condition.

The downregulation of OPN inhibits proliferation and migration and regulate activation of Erk1/2 in ECA-109 cells.

Osteopontin (OPN) involves in tumor formation, and strongly correlated with the tumor progression. It was overexpressed in human esophageal squamous cell carcinoma (ESCC). To study the molecular mechanisms of OPN in ESCC, we examined its roles in inhibiting proliferation and invasion of ECA-109 (esophageal squamous cell carcinoma) cells. The expression of OPN gene was knockdown by RNA interference (RNAi) in the Eca-109 cell. The transcription level of OPN was to detect by reverse transcription-quantitative PCR (RT-qPCR). Western blot assay was performed to detect the expression of OPN, Caspase-3,Caspase-8, Caspase-9, ERK1/2, phospho-ERK1/2 and MMP2 after RNAi. The cell proliferation and apoptosis were detected by MTT and Hoechst33342 assay. Transwell inserts was used for detecting ECA-109 cell's migration ability. The results shown that the level of OPN mRNA and protein was significantly reduced after RNAi. Proliferation and migration of cell line (ECA-109) was significantly inhibited in vitro. The protein phosphorylation and activation of ERK1/2 in the OPN RNAi group reduced significantly than the negative control groups. In Conclusion, the proliferation and migration of human ESCC can be inhibited by RNAi-targeting OPN. OPN can promote the expression of MMP2 through the ERK signaling pathways. OPN could serve as a potential therapeutic target for human ESCC.

Role of osteopontin in the regulation of human bladder cancer proliferation and migration in T24 cells.

Osteopontin (OPN), a secreted acid glycoprotein with a variety of functions, promotes tumor proliferation, differentiation, invasion and metastasis. The aim of the current study was to investigate whether OPN may serve as a potential therapeutic target for human bladder cancer. RNA interference (RNAi) was performed to downregulate the expression of the OPN gene in T24 human bladder cancer cells. The mRNA and protein expression levels of OPN following RNAi were determined using reverse transcription­quantitative polymerase chain reaction and western blot analysis, respectively. In addition, the cell cycle progression, apoptosis and proliferation were investigated using by flow cytometric analysis and MTT assay. The cell invasion ability was measured using a Matrigel transwell assay. The mRNA and protein expression levels of OPN were found to be significantly downregulated following RNAi. The proliferation and invasion of T24 cells were significantly inhibited in vitro. In conclusion, RNAi­targeting OPN may inhibit the proliferation, invasion and tumorigenicity of human bladder cancer cells. Therefore, OPN may serve as a potential therapeutic target for human bladder cancer.