ABSTRACT
Platelet counts have been reported to be closely related to distant metastasis of many malignant tumors. Our previous study showed that elevated peripheral blood platelet counts may be an adverse prognostic factor of anaplastic thyroid carcinoma (ATC) patients, indicating that platelets may promote ATC progression. In the present study, we aimed to identify the role of platelets in ATC cell invasion and migration and to explore the underlying mechanisms. We found that platelets can promote the invasive and migratory of ATC cells, which may be related to the interaction between activated platelet-secreted chemokine (C-C motif) ligand 3 (CCL3) and its receptor CCR5. The interaction was shown to induce the upregulation of matrix metalloproteinase (MMP)-1 via NF-κB pathway. These findings could provide a new idea for the research of targeted platelets to inhibit tumor metastasis.
Subject(s)
Blood Platelets/metabolism , Chemokine CCL3/metabolism , Matrix Metalloproteinase 1/metabolism , Receptors, CCR5/metabolism , Thyroid Carcinoma, Anaplastic/metabolism , Thyroid Neoplasms/metabolism , Blood Platelets/pathology , Cell Line, Tumor , Cell Movement , HEK293 Cells , Humans , NF-kappa B/metabolism , Platelet Activation , Thyroid Carcinoma, Anaplastic/pathology , Thyroid Neoplasms/pathologyABSTRACT
The role of autophagy in tongue squamous cell carcinoma (TSCC) cisplatin resistance is unclear. We aimed to identify a possible synergistic effect of autophagy inhibitors and cisplatin in TSCC cells and explore the underlying mechanism. Our results indicate that autophagic flux was high in TSCC cells; Autophagy inhibitor bafilomycin A1 increased cisplatin cytotoxicity in TSCC cells by inhibiting lysosomal uptake of platinum and enhancing intracellular platinum ion binding to DNA; Autophagy gene (Atg5) knockout in TSCC cells did not duplicate the above-mentioned sensitization of bafilomycin A1. Furthermore, we found that cisplatin resistance of TSCC cells was related to cisplatin inducing lysosome biogenesis in a TFEB-dependent manner, which was regulated by c-Abl. In summary, this is the first study to show that Bafilomycin A1 increases the sensitivity of TSCC cells to cisplatin by inhibiting lysosomal function but not autophagy. Lysosomes may be a potential target to increase cisplatin cytotoxicity toward TSCC cells.
Subject(s)
Carcinoma, Squamous Cell/metabolism , Cisplatin/pharmacology , Lysosomes/drug effects , Macrolides/pharmacology , Platinum/metabolism , Tongue Neoplasms/metabolism , Autophagy , Autophagy-Related Protein 5/genetics , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/genetics , Cell Line, Tumor , Drug Resistance, Neoplasm/drug effects , Drug Synergism , Gene Expression Regulation, Neoplastic/drug effects , Gene Knockout Techniques , Humans , Lysosomes/genetics , Lysosomes/metabolism , Proto-Oncogene Proteins c-abl/metabolism , Tongue Neoplasms/drug therapy , Tongue Neoplasms/geneticsABSTRACT
In the title compound, [Cu(NO(3))(2)(C(14)H(36)N(6))](NO(3))(2)·4H(2)O, the Cu(II) atom, lying on an inversion center, is six-coordinated in a distorted octa-hedral environment by four N atoms from a centrosymmetric 14-membered tetra-aza-cyclo-tetra-decane macrocyclic ligand and two O atoms from two nitrate anions. The supra-molecular network is consolidated by extensive O-Hâ¯O and N-Hâ¯O hydrogen-bonding inter-actions.
