| 1 | Regulatory effects of antitumor agent matrine on FOXO and PI3K-AKT pathway in castration-resistant prostate cancer cells显示文摘We previously demonstrated that matrine could inhibit the proliferating, migrating, as well as invading processes of both PC-3 and DU145 cells. However, the underlying molecular mechanisms have not yet been clearly defined. In this study, using various techniques such as high throughput sequencing technology, bioinformatics, quantitative real-time PCR, and immunoblot analysis,we aimed to understand whether matrine serves as a novel regulator of FOXO and PI3K-AKT signaling pathway. DU145 and PC-3 cell lines were cultured for 24 h in vitro. Cells were treated with either matrine or control serum for 48 h, followed by extraction of total RNA. The RNA was sequenced using HiSeq 2500 high-throughput sequencing platform (Illumina). A gene library was established and quality analysis of read data carried out. Integrated database from the website DAVID was used to analyze Gene Ontology (GO), and Kyoto encyclopedia of genes and genomes (KEGG) pathway of differential genes was used for pathway analysis, screening for fold differences of more than two times. The FOXO and PI3K-AKT signaling pathways were screened, and expression levels of mRNA and core protein detected by real-time PCR and immunoblotting, respectively. High throughput sequencing and GO analysis revealed that differentially expressed genes before and after treatment played an important role in cell metabolic process, growth process, anatomical structure formation, cellular component organization, and biological regulation. KEGG signal pathway analysis revealed that FOXO and PI3K-AKT signal pathways had a significant difference between before and after matrine-treated androgen-independent prostate cancer cells PC-3 and DU145. Real-time PCR showed that matrine treatment led to a significant increase in the expression levels of FOXO1A, FOXO3A, FOXO4, and FOXO6 in DU145 and PC-3 cells (P<0.01 or P<0.05), whereas the PI3K expression levels decreased (P<0.01). Similarly, immunoblotting revealed a significant increase (P<0.05) in the expression levels of FOXO1A FOXO3A, FOXO4, and FOXO6 in both PC-3 and DU145 cells, whereas PI3K expression levels decreased (P<0.05). Matrine had a broad regulating effect on the mRNA expression profiles of both PC-3 and DU145 cells. Matrine may inhibit cell proliferation, migration, as well as invasion, and induce apoptosis in both PC-3 and DU145 cells through FOXO and PI3K-AKT signaling pathways. Matrine could therefore be used as a complementary drug to present chemotherapeutic agents, for treating androgen-independent prostate cancer. | Qi Li HaiH uang Zheng He Yi Sun Yufeng Tang Xiaohong Shang Chengbin Wang | 2018 | Science China(Life Sciences)2018，61，5： | 9 |
| 2 | A strategy to enhance the insecticidal potency of Vip3Aa by introducing additional cleavage sites to increase its proteolytic activation efficiency显示文摘Microbially derived,protein-based biopesticides have become a vital element in pest management strategies.Vip3 family proteins from Bacillus thuringiensis have distinct characteristics from known insecticidal Cry toxins and show efficient insecticidal activity against several detrimental lepidopteran pests.They are considered to be a promising toxic candidate for the management of various detrimental pests.In this study,we found that in addition to the preliminary digestion sites lysine,there are multiple cleavage activation sites in the linker region between domain I(DI)and DII of Vip3Aa.We further demonstrated that by adding more cleavage sites between DI and DII of Vip3Aa,its proteolysis efficiency by midgut proteases can be significantly increased,and correspondingly enhance its insecticidal activity against Spodoptera frugiperda and Helicoverpa armigera larvae.Our study promotes the understanding of the insecticidal mechanism of Vip3 proteins and illustrates an eas-ily implementable strategy to increase the insecticidal potency of Vip3Aa.This facilitates their potential future development and efficient application for sustainable agriculture. | Kun Jiang Zhe Chen Yiting Shi Yuanrong Zang Chengbin Shang Xi Huang Jiahe Zang Zhudong Bai Xuyao Jiao Jun Cai Xiang Gao | 2023 | Engineering Microbiology2023，3，4： | 1 |
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