1.Effects of total flavonoids from Cycas Revolute on expression of VEGF,bFGF,HIF-1α and NF-κB in model mice of Lewis lung cancer
Shaohui WANG ; Sibu MA ; Yu YAN ; Zhekang CHENG ; Yachen ZHANG ; Tongxiang LIU
Chinese Journal of Immunology 2017;33(7):1029-1034
Objective:To investigate the effects of total flavonoids from Cycas Revolute on expression of vascular endothelial growth factor (VEGF),basic fibroblast growth factor (bFGF),Hypoxia inducible factor-1α (HIF-1α) and nuclear factor-κB(NF-κB) in model mice of Lewis lung cancer.Methods: The expressions of VEGF,bFGF,HIF-1α and NF-κB in tumor tissues were detected by immunohistochemistry and Western blot.The expression of VEGF,VEGF and NF-κB in tumor tissues were detected by fluorescent quantitative PCR.BFGF,HIF-1α and NF-κB mRNA were detected by immunohistochemistry.Results: The results of immunohis-tochemistry,Western blot and Real-time PCR showed that the results were basically the same,compared with model group,the expression of VEGF,bFGF,HIF-1α,NF-κB mRNA and the expression of VEGF,bFGF,HIF-1α and NF-κB were decreased,the difference was highly significant (P<0.05).Conclusion: The mechanism of total flavonoids from Cycas Revolute in the treatment of lung cancer may be through inhibition of the expression of VEGF,bFGF,HIF-1α,NF-κB in invasion and metastasis,and further inhibit the expression of VEGF,bFGF,HIF-1α and NF-κB in invasion and metastasis-related proteins,thus play a role of anti-lung cancer invasion and metastasis.
2.Menthol-modified casein nanoparticles loading 10-hydroxycamptothecin for glioma targeting therapy.
Caifang GAO ; Jianming LIANG ; Ying ZHU ; Chengli LING ; Zhekang CHENG ; Ruixiang LI ; Jing QIN ; Weigen LU ; Jianxin WANG
Acta Pharmaceutica Sinica B 2019;9(4):843-857
Chemotherapy outcomes for the treatment of glioma remains unsatisfactory due to the inefficient drug transport across the blood-brain barrier (BBB) and insufficient drug accumulation in the tumor region. Although many approaches, including various nanosystems, have been developed to promote the distribution of chemotherapeutics in the brain tumor, the delivery efficiency and the possible damage to the normal brain function still greatly restrict the clinical application of the nanocarriers. Therefore, it is urgent and necessary to discover more safe and effective BBB penetration and glioma-targeting strategies. In the present study, menthol, one of the strongest BBB penetration enhancers screened from traditional Chinese medicine, was conjugated to casein, a natural food protein with brain targeting capability. Then the conjugate self-assembled into the nanoparticles to load anti-cancer drugs. The nanoparticles were characterized to have appropriate size, spheroid shape and high loading drug capacity. Tumor spheroid penetration experiments demonstrated that penetration ability of menthol-modified casein nanoparticles (M-CA-NP) into the tumor were much deeper than that of unmodified nanoparticles. imaging further verified that M-CA-NPs exhibited higher brain tumor distribution than unmodified nanoparticles. The median survival time of glioma-bearing mice treated with HCPT-M-CA-NPs was significantly prolonged than those treated with free HCPT or HCPT-CA-NPs. HE staining of the organs indicated the safety of the nanoparticles. Therefore, the study combined the advantages of traditional Chinese medicine strategy with modern delivery technology for brain targeting, and provide a safe and effective approach for glioma therapy.