Aloperine Prevents Migration, Invasion, and Adhesion by Upregulating TIMP-4 in Human Bladder Cancer Cells.

BACKGROUND: Aloperine (ALO) is an important active component of quinolizidine alkaloids in Sophora flavescens A and Sophora alopecuroides L, and has effective anticancer activity against multiple cancers. However, the influence and mechanism of ALO on migration, invasion, and adhesion in bladder cancer cells remain unclear. OBJECTIVE: The aim of this study is to determine the anticancer effect of ALO on migration, invasion, and adhesion in bladder cancer cells and to investigate its potential TIMP-4-related mechanism. METHODS: Cell viability, cytotoxicity, wound healing, Transwell invasion, cell adhesion, real-time qPCR, western blot, and ELISA assays were performed to analyze the effect of ALO on migration, invasion, and adhesion in bladder cancer 5637 and UM-UC-3 cells. Furthermore, the anti-TIMP-4 antibody was used to explore the potential effect on ALO-inhibited bladder cancer cells. RESULTS: We have found that ALO significantly suppressed migration, invasion, and adhesion in bladder cancer cells. Furthermore, ALO could downregulate the expression of MMP-2 and MMP-9 mRNAs and proteins, and increase the expression of TIMP-4 mRNA and protein. Moreover, the anti- TIMP-4 antibody reversed the prevention of migration, invasion, and adhesion in ALO-treated bladder cancer cells. CONCLUSION: The data in this study suggest that ALO suppressed migration, invasion, and adhesion in bladder cancer cells by upregulating the expression of TIMP-4.

Host-Guest Interaction-Based Dual response core/shell nanoparticles as efficient siRNA carrier for killing breast cancer cells.

How to overcome multiple obstacles to achieve the efficient and safe delivery of therapeutic genes is still the key to gene therapy. To address this issue, a cationic carrier consisting of polyamide-amine (HPAA-peptide-Fc) modified by an enzyme-responsive polypeptide as the core and hyperbranched polyglycerol derivative (CD-HPG) as the shell was synthesized by self-assembly. The obtained HPAA-peptide-HPG could form the compact nanocomplex with siPlk1, thus confirming the stable load of genes and subsequent targeted gene delivery. And the nanogenes could significantly induce apoptotic effect via the down-expression of Plk1 protein in breast cancer cells. Moreover, compared to polyethylenimine, HPAA-peptide-HPG exhibited superior biocompatibility through hemolysis and cell viability assays because of the shielding function of CD-HPG, thereby being beneficial to increasing the circulation time of the complex when administrated in vivo. Such an efficient and safe gene delivery complex (HPAA-peptide-HPG) presents a good example of rational design of cationic supramolecular vesicles for stimulus-responsive siRNA transport, which should be encouraged in cancer gene therapy.

Codelivery of epigallocatechin-3-gallate and diallyl trisulfide by near-infrared light-responsive mesoporous polydopamine nanoparticles for enhanced antitumor efficacy.

Green tea extract epigallocatechin-3-gallate (EGCG), as a kind of natural active compounds, has become a research hotspot in cancer treatment. However, poor stability, low bioavailability and antitumor efficacy limit the application of EGCG. In this study, mesoporous dopamine (MPDA) with high drug loading and good biocompatibility loaded EGCG, garlic extract diallyl trisulfide (DATS) and photosensitizer (indocyanine green, ICG) by π-π stacking and hydrophobic-hydrophobic interaction, and the nano-system involved filling the mesoporous of the MPDA with phase change material (1-tetradecanol, 1-TD) molecules, which acted as a thermosensitive gatekeeper. The results indicated that MPDA-ICG@TD has an excellent photothermal effect and good stability. Due to the solid-liquid phase transition characteristics of the phase change material, MPDA-ICG@TD could control the release of drugs under near-infrared laser irradiation. Besides, cytotoxicity and apoptosis experiments showed that MPDA-ICG/EGCG/DATS@TD could be efficiently inhibited 4T1 cell proliferation and accelerate cell apoptosis than use diallyl trisulfide or EGCG alone, which means that the combination of natural active compounds EGCG and diallyl trisulfide has excellent synergy and can effectively improve the antitumor effect of EGCG. Moreover, this nano-system exhibited non-toxicity and good blood compatibility. This study provides a promising and effective strategy for improving the antitumor efficacy of natural active compound EGCG.