gambogic-acid and Adenocarcinoma

This study aimed to develop a novel type of multilayer micelle using protamine (PRM) and hyaluronic acid (HA) for the delivery of gambogic acid (GA). GA-loaded micelles (GA-M) were simply andrapidly prepared using lecithin/solutol HS15 using a film-dispersion method. PRM and HA were added in sequence to form layer-by-layer self-assembled micelles (HA-PRM-GA-M), in which particle size, zeta potential, particle morphology, drug loading, encapsulation efficiency, and in vitro release were investigated. Surface charge reversal demonstrated that rapid HA detachment exposed PRM, leading to activation of a "proton sponge" effect in the hyaluronidase (HAase)-rich tumor microenvironment. Compared with coumarin 6-loaded micelles (C6-M), more efficient intracellular trafficking was observed for HA-PRM-C6-M, which is associated with the endosomal/lysosomal escaping ability of the exposed PRM. In vivo imaging showed increased enrichment of near infrared fluorescent dye (DIR)-loaded HA-PRM-DIR-M at the tumor site, suggesting that HA enhanced the active tumor targeting of GA. Furthermore, HA-PRM-GA-M showed the stronger antitumor activity than GA and GA-M against human lung adenocarcinoma (A549) tumor xenografts in nude mice. In summary, our findings show the potential of HA-PRM-GA-M as a novel intravenous drug carrier for the treatment of lung cancer.

Topics: A549 Cells; Adenocarcinoma; Adenocarcinoma of Lung; Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Cell Movement; Cell Proliferation; Drug Carriers; Drug Compounding; Drug Liberation; Endocytosis; Humans; Hyaluronic Acid; Injections, Intravenous; Lung Neoplasms; Male; Mice, Nude; Micelles; Particle Size; Protamines; Solubility; Surface Properties; Technology, Pharmaceutical; Time Factors; Tissue Distribution; Xanthones; Xenograft Model Antitumor Assays

To investigate the effects of gambogic acid (GA) on the proliferation inhibition and apoptosis induction in Human lung adenocarcinoma A549 cells in vitro, as well as the regulation of steroid receptor coactivator-3 (SRC-3) to explore the relationship between them.. The effect of GA on the growth of A549 cells was studied by MTT assay. Apoptosis was detected by Hoechst 33258 staining. The localization of SRC-3 was determined by confocal laser scanning microscopy. Western blot and RT-PCR technique were applied to assess the expression of SRC-3.. GA presented a striking proliferation inhibition potency on A549 cells in vitro, as well as apoptosis induction activity in a time- and dose-dependent manner. The IC(50) value for 24 h was (3.17 +/- 0.13) micromol/L. Overexpression of SRC-3 was found in A549 cells, whereas the SRC-3 protein and mRNA expression levels were significantly downregulated in A549 cells induced by GA in a dose-dependent manner. The location of SRC-3 was situated mainly in the cell nuclei.. GA exhibits a potent proliferation inhibition and apoptosis induction in human lung adenocarcinoma A549 cells, which might correspond to the downregulation of the expression of SRC-3. Thus, it promises to be a new target drug for lung cancer treatment.

Topics: Adenocarcinoma; Antineoplastic Agents, Phytogenic; Apoptosis; Cell Line, Tumor; Cell Nucleus; Cell Proliferation; Dose-Response Relationship, Drug; Down-Regulation; Humans; Lung Neoplasms; Nuclear Receptor Coactivator 3; RNA, Messenger; Xanthones