ABSTRACT
BACKGROUND/AIM: Phosphaplatin platinum (IV) (RRD4) complex has exceptional antitumor properties. The aim of this study was to investigate the effects and the mechanism of action of free and liposome-encapsulated RRD4 in breast cancer. MATERIALS AND METHODS: Liposome-encapsulated RRD4 prepared by thin-film dehydration: hydration and free RRD4 were tested in vivo and in vitro against 4T1 breast cancer cells. Cell proliferation, migration and viability were determined. Tissue and cell production and expression of pigment epithelium-derived factor (PEDF) were assessed by ELISA and western blot. 4T1 cells treated with PEDF siRNA were evaluated for viability and apoptosis. RESULTS: RRD4 inhibited tumor growth and prevented distant metastasis. Liposome formulation enhanced this therapeutic benefit without increasing toxicity and prolonged RRD4 retention in tumor tissues. In vitro, RRD4 induced 4T1 apoptosis through up-regulation of FAS, BAX, and PUMA, and down-regulation of BCL2. RRD4 facilitates a FAS-intrinsic signaling mechanism. PEDF up-regulation represents another antitumor mechanism associated with this phosphaplatin compound. DISCUSSION: Free RRD4 or formulated into liposomes, are excellent candidates for adjuvant therapy against breast tumor growth and metastasis.
Subject(s)
Antineoplastic Agents/pharmacology , Eye Proteins/metabolism , Liposomes/pharmacology , Mammary Neoplasms, Experimental/drug therapy , Nerve Growth Factors/metabolism , Organoplatinum Compounds/pharmacology , Serpins/metabolism , Animals , Antineoplastic Agents/administration & dosage , Cell Line, Tumor , Cell Proliferation/drug effects , Eye Proteins/genetics , Female , Gene Knockdown Techniques , Liposomes/administration & dosage , Liposomes/chemistry , Mammary Neoplasms, Experimental/metabolism , Mice, Inbred BALB C , Nerve Growth Factors/genetics , Organoplatinum Compounds/administration & dosage , Serpins/genetics , Up-Regulation/drug effectsABSTRACT
Objective To investigate the expression of TRIM28 and p16 in esophageal squamous cell car-cinoma(ESCC)and explore the possible correlation with them and clinicopathological characteristics. Methods The expression level of TRIM28 and p16 were measured by immunohistochemistry S-P in 136 cases with ESCC and 37 cases with normal esophageal mucosa,selected from the First Affiliated Hospital of Hebei North University De-partment of Pathology.The relationship between them and the clinical-pathological features was also analyzed.The localization of TRIM28 and p16 protein in ESCC was detected by immunofluorescence. Results(1)The positive rates of TRIM28 and p16 in ESCC were 91.2%and 32.4%,respectively,whereas in normal esophageal mucosa the corresponding rates were 24% and 57%,respectively.(2)Immunofluorescence results showed that TRIM28 and p16 protein were all mainly distributed in the nucleus of ESCC.(3)The abnormal expression of TRIM28 and p16 protein were all related to the invasion depth,TNM staging and lymph node metastasis in ESCC(P < 0.05).(4) The expression of TRIM28 was negatively correlated to the expression of p16 in ESCC(r =-0.284,P = 0.001). Conclusions The abnormal expression of TRIM28 and p16 may have synergistic effect on the initiation and devel-opment of ESCC.Co-detection of the expression of them may be useful for diagnosis of ESCC and guiding the clini-cal therapy.
ABSTRACT
Background Clinical studies indicated that the pathogenesis of most corneal dystrophy is associated with the mutation of the transforming growth factor beta-induced (TGFBI) gene.However,the molecular mechanism of mutated TGFBI gene in corneal dystrophy is unclear. Objective The present study was to investigate the expression of the TGFBI gene in human corneal tissue and cells in vitro.MethodsHuman corneal epithelial cells and keratocytes were cultured and passaged,and donor corneal tissue was obtained for the section preparation.RT-PCR was used to detect the expression of TGFBI mRNA in human corneal tissue and cells.Immunofluorescence was used to test the expression of the TGFBI protein in the human corneal tissue,and immunohistochemistry was used to test the expression of the TGFBI protein in human corneal epithelial cells and corneal stromal cells.ResultsRT-PCR analysis showed that TGFBI mRNA could be detected as a 1274 bp band in human corneal tissue and corneal stromal cells,but no TGFBI mRNA was observed in corneal epithelial cells.Immunofluorescence assay revealed that corneal stromal cells were positive ly expressed for the TGFBI protein,but the corneal epithelial cells did not express the TGFBI protein.Immunohistochemistry indicated that the expression of TGFBI was detected the red fluoressence in the cytoplasm of corneal stromal cells;however,no positive response was found in corneal epithelial cells.ConclusionsThe expression of the TGFBI gene occurs in human corneal stromal cells but not in the corneal epithelial cells.This result might be of helpful for studying the function and role of TGFBI gene in pathogenesis of corneal dystrophy.
