The active compounds isolated from Black pepper have anticancer effects, but the bioactivity of Black pepper essential oil (BP‐EO) is rarely studied. BP‐EO has poor stability and a suitable dose form should be prepared for in vivo delivery. Triple negative breast cancer (TNBC) has attracted more and more attention due to its high mitotic index, high metastasis rate and poor prognosis. In this study, the composition of BP‐EO was analyzed by gas chromatography–mass spectrometry (GC–MS), and nanoparticles (NPs) loaded with BP‐EO were prepared by nanoprecipitation method using Eudragit L100 as a carrier. We investigated the preparation, characterization, stability and in vitro release of nanoparticles. MTT assay, cell wound healing, Transwell invasion assay and Western blot were used to study the anti‐tumor effect and mechanism of MDA‐MB‐231 cells. The GC–MS analysis identified a total of 33 compounds among which alkenes account for 63.55%. The prepared BP‐EO NPs exhibited nanoscale morphology, good stability and pH‐responsive and sustained release character which is suitable for in vivo delivery. BP‐EO NPs significantly inhibited the proliferation, migration and invasion of MDA‐MB‐231 cells. Furthermore, BP‐EO NPs significantly inhibited the expressions of Wnt and β‐catenin and significantly activated the expression of GSK‐3β in MDA‐MB‐231 cells. Therefore, BP‐EO NPs prepared in this study provide a new effective strategy for the treatment of TNBC. Practical applications Black pepper is rich in essential oil and has excellent antioxidant and antibacterial activities. However, the anti‐tumor activity of BP‐EO has not been studied. In this study, we found that BP‐EO has excellent anticancer activity. To achieve effective encapsulation of black pepper essential oil and an excellent anti‐triple negative breast cancer activity, nanoparticles loaded with BP‐EO were prepared using Eudragit L100 as the carrier by the nanoprecipitation method. The in vitro study revealed that BP‐EO NPs inhibited proliferation, migration and invasion of MDA‐MB‐231 cells via inhibiting the Wnt/β‐Catenin signaling pathway. This study provides new ideas and innovations for the treatment of invasive triple negative breast cancer in the future. At the same time, we will further reveal the application potential, pharmacokinetic characteristics and precise mechanism of BP‐EO NPs in vivo in subsequent studies.
Background: BRD4 is a member of the bromodomain and extra terminal domain (BET) family of proteins, containing two bromodomains and one extra terminal domain, and is overexpressed in several human malignancies. However, its expression in gastric cancer has not yet been well illustrated. Objective: This study aimed to elucidate the overexpression of BRD4 in gastric cancer and its clinical significance as a novel therapeutic target. Methods: Fresh gastric cancer tissues and paraffin-embedded specimens of gastric cancer patients were collected, and the BRD4 expression was examined by Western Blot Analysis (WB) and Immunohistochemistry Analysis (IHC), respectively. The possible relationship between BRD4 expression and the clinicopathological features as well as survival in gastric cancer patients was analyzed. The effect of BRD4 silencing on human gastric cancer cell lines was investigated by MTT assay, WB, wound healing assay, and Transwell invasion. Results: The results showed that the expression level in tumor tissues and adjacent tissues was significantly higher than that in normal tissues, respectively (P<0.01). BRD4 expression level in gastric cancer tissues was strongly correlated with the degree of tumor differentiated degree (P=0.033), regional lymph nodes metastasis (P=0.038), clinical staging (P=0.002), and survival situation (P=0.000), while the gender (P=0.564), age (P=0.926) and infiltrating depth (P=0.619) of patients were not associated. Increased BRD4 expression resulted in poor overall survival (p=0.003). In in vitro assays, BRD4 small interfering RNA resulted in significantly decreased BRD4 protein expression, therefore inhibiting proliferation, migration, and invasion of gastric cancer cells. Conclusion: BRD4 might be a novel biomarker for the early diagnosis, prognosis, and therapeutic target in gastric cancer.
With the development of newer biomarkers in the diagnosis of gastric cancer (GC), therapeutic targets are emerging and molecular-targeted therapy is in progress RNA interference has emerged as a promising method of gene targeting therapy. However, bare small interfering RNA (siRNA) is unstable and susceptible to degradation, so developing vectors for siRNA delivery is the focus of our research. We developed LMWP modified PEG-SS-PEI to deliver siRNA targeting BRD4 (L-NPs) for GC therapy. L-NPs were prepared by electrostatic interaction and characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The release characteristics, cellular uptake and intracellular localization were also investigated. The in vitro anticancer activity of the prepared nanoparticles was analysed by MTT, Transwell invasion and wound healing assay. Western blot was used to detect the effect of gene silencing. The results showed that the optimal N/P was 30 and the prepared L-NPs uniformly distributed in the system with a spherical and regular shape. L-NPs exhibited an accelerated release in GSH-containing media from 12h to 24h. The uptake of L-NPs was enhanced and mainly co-localized in the lysosomes. After 6h incubation, LMWP modified PEG-SS-PEI helped siRNA escape from the lysosomes and diffused into the cytoplasm. L-NPs significantly in hibited the proliferation, migration and invasion of cells. This might be related with the silence of BRD4, then inhibition of PI3K/Akt and c-Myc. Our results demonstrate that L-NPs are a novel delivery system with anticancer, which may provide a more effective strategy for GC treatment.
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