ABSTRACT
The electrospun nanofiber system is correlated with high efficacy of drug delivery. This study aims to investigate the effect of nanofiber-based delivery of evodiamine, an indole alkaloid derived from Rutaceae plants Evodia rutaecarpa (Juss.) Benth, on intrahepatic cholangiocarcinoma (ICC), as well as to explore the molecular mechanisms. An electrospun nanofiber system carrying evodiamine was generated. Compared to evodiamine treatment alone, the nano-evodiamine exhibited more pronounced effects on suppressing proliferation, colony formation, invasiveness, migration, apoptosis resistance, cell cycle progression, and in vivo tumorigenesis of two ICC cell lines (HUCC-T1 and RBE). ICC cells exhibited increased expression of histone deacetylase 4 (HDAC4) while decreased tropomyosin 1 (TPM1). HDAC4 suppressed TPM1 expression by removing H3K9ac modifications from its promoter. Nano-evodiamine reduced HDAC4 protein levels in ICC cells, thus promoting transcription and expression of TPM1. Either overexpression of HDAC4 or downregulation of TPM1 negated the tumor-suppressive effects of nano-evodiamine. Collectively, this study demonstrates that the electrospun nanofiber system enhances the efficiency of evodiamine. Additionally, evodiamine suppresses the malignant properties of ICC cells. The findings may provide fresh insights into the application of electrospun nanofiber system for drug delivery and the effects of evodiamine on tumor suppression.
Subject(s)
Cholangiocarcinoma , Drug Delivery Systems , Histone Deacetylases , Nanofibers , Tropomyosin , Tropomyosin/genetics , Tropomyosin/metabolism , Humans , Cholangiocarcinoma/pathology , Cholangiocarcinoma/drug therapy , Cholangiocarcinoma/genetics , Histone Deacetylases/metabolism , Histone Deacetylases/genetics , Cell Line, Tumor , Quinazolines/pharmacology , Cell Proliferation/drug effects , Cell Proliferation/genetics , Bile Duct Neoplasms/pathology , Bile Duct Neoplasms/drug therapy , Bile Duct Neoplasms/genetics , Transcription, Genetic/drug effects , Transcription, Genetic/genetics , Gene Expression/drug effects , Gene Expression/genetics , Molecular Targeted Therapy , Apoptosis/drug effects , Apoptosis/genetics , Repressor ProteinsABSTRACT
Slow skeletal muscle troponin T (TNNT1) has been reported to be correlated with several cancers, but there are no evidences proving that TNNT1 is required in colon adenocarcinoma (COAD). TNNT1 expression in COAD tissues and its prognostic significance were acquired from TCGA database. The proliferative, migratory, and invasive abilities of COAD cells were detected by CCK-8 and transwell assays, respectively. Correlations between TNNT1 and epithelial-mesenchymal transition (EMT)-related markers were determined using western blotting and Pearson's analysis. Our results stated that TNNT1 expression was high-regulated in COAD tissues, which was related with unfavorable prognosis of COAD patients. Functional analyses suggested that TNNT1 promoted the cellular behaviors. Moreover, aberrant expression of TNNT1 affected the expression level of EMT-related proteins. And TNNT1 was negatively linked with E-cadherin. In conclusion, our findings indicated that TNNT1 may promote the progression of COAD, mediating EMT process, and thus shed a novel light on COAD therapeutic treatments.
Subject(s)
Adenocarcinoma/pathology , Cell Movement , Cell Proliferation , Colonic Neoplasms/pathology , Epithelial-Mesenchymal Transition , Troponin T/genetics , Troponin T/metabolism , Antigens, CD/metabolism , Cadherins/metabolism , Databases, Genetic , Gene Expression , Gene Knockdown Techniques , HCT116 Cells , Humans , Neoplasm Invasiveness , Prognosis , TransfectionABSTRACT
The aim of this study was to elucidate the potential impact of "D2 plus" lymphadenectomy on the long-term survival of distal gastric cancer (GC) patients with clinical serosa invasion. A total of 394 distal GC patients with clinical serosa invasion who underwent at least standard D2 lymphadenectomy were enrolled. Patients were categorized into two groups according to the extent of lymphadenectomy: D2 group and "D2 plus" group. Propensity score matching was used to adjust for the differences in baseline characteristics. In the multivariate analysis for the whole study series, extent of lymphadenectomy was an independent prognostic factor for GC patients (P = 0.011). With the strata analysis, the significant prognostic differences between the two groups were only observed in patients at the IIIa-b or N1-3a stages. After matching, patients in "D2 plus" group still demonstrated a significantly higher 5-year overall survival rate than those in D2 group (55.3% versus 43.9%, P = 0.042). The common therapeutic value index of No. 12b, No. 12p, No. 14v and No. 13 LNs was 4.6, which was close to that of No. 5 LN station. In conclusion, "D2 plus" lymphadenectomy may be associated with improved overall survival in distal GC with clinical serosa invasion.