Background: Oxaliplatin (OXA) resistance is a main obstacle to the chemotherapy of colorectal cancer (CRC). Epithelial-mesenchymal transition (EMT), which is mainly regulated by TGF-β/Smad signaling pathway, has gradually been recognized as an important mechanism for tumor chemoresistance. Studies have shown that curcumin regulated EMT processes in many human cancers. However, whether curcumin could regulate OXA resistance in CRC through modulating TGF-β/Smad signaling-mediated EMT remains unclear. Methods: In an attempt to investigate the effect of curcumin on OXA resistance in CRC, OXA-resistant cell line HCT116/OXA was established firstly. The effect of curcumin on cell proliferation was evaluated by MTT assay and Ki67 immunofluorescence staining, respectively. Cell apoptosis was evaluated by flow cytometry. In addition, transwell assay was used to detect the effect of curcumin on cell invasion and the activation of TGF-β/Smad signaling was examined by immunofluorescence and Western blot. Moreover, the therapeutic potential of curcumin was further examined in vivo using a CRC animal model. Results: The OXA-resistant cell line HCT116/OXA was successfully established, and combination of OXA with curcumin reduced OXA resistance in vitro. Besides, the combination treatment inhibited the expressions of p-p65 and Bcl-2, but increased the level of active-caspase3. In addition, curcumin inhibited EMT via regulation of TGF-β/Smad2/3 signaling pathway. Moreover, in vivo study confirmed curcumin could reverse OXA resistance in CRC. Conclusion: Our study indicated that curcumin could reserve OXA resistance in CRC through dampening TGF-β/Smads signaling in vitro and in vivo.
BackgroundLong noncoding RNAs (lncRNAs) have been implicated in several human cancers. The expression profile and underlying mechanism of the lncRNA MAP3K1-2 in gastric cancer (GC) are poorly understood.MethodsSixty-one patients with GC were recruited from Shanghai Baoshan Luo Dian Hospital (Shanghai, China). Tumor tissues and paired normal tissues (5 cm adjacent to the tumor) were obtained. Expression of lncRNA MAP3K1-2 in GC cell lines was examined using quantitative real-time polymerase chain reaction. Protein expression was detected using Western blot. Cell cycle analysis was assessed using flow cytometry. Cell proliferation was assessed using soft agar assays, and cell invasion was assessed using Transwell assays.ResultsThe expression level of lncRNA MAP3K1-2 was upregulated in GC cells and markedly higher in poorly differentiated cell lines. Silencing treatment of lncRNA MAP3K1-2 significantly inhibited cell proliferation and invasion in GC. In addition, knockdown of lncRNA MAP3K1-2 significantly inhibited the function of important genes in the MAPK signaling pathway. Higher expression of lncRNA MAP3K1-2 was often associated with poorer prognosis in patients with GC.ConclusionslncRNA MAP3K1-2 is a critical effector in GC tumorigenesis and progression, representing novel therapeutic targets. High lncRNA MAP3K1-2 expression may serve as a novel independent prognostic marker for predicting the outcome of GC.
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