1. Preparation and the effect of antitumor of DNA plasmid lipidosome vaccine based VEGFR2 extracellular region by immunization activated in vitro
Minfang CHEN ; Liyun XIE ; Fenfen XU ; Aixiao XIA ; Zhong LIN ; Lihua CHEN
Chinese Journal of Clinical Pharmacology and Therapeutics 2021;26(1):24-29
AIM: The DNA plasmid lipidosome (LP) vaccine based VEGFR2 extracellular region (exVEGFR2) was prepared in order to provide a new approach for cancer active immunotherapy. METHODS: High fidelity PCR was used to amplify the target sequence of exVEGFR2 with two restriction site of Kpn and Xba. The plasmid of pCMV/exVEGFR2 was constructed by connected exVEGFR2 with pCMV empty plasmid. The activity of immune activation was detected by ELISA. CTLs mediated cytotoxic activity was analyzed by
2.AKT inhibitor Hu7691 induces differentiation of neuroblastoma cells.
Shaowei BING ; Senfeng XIANG ; Zhimei XIA ; Yilong WANG ; Zhonghai GUAN ; Jinxin CHE ; Aixiao XU ; Xiaowu DONG ; Ji CAO ; Bo YANG ; Jinhu WANG ; Qiaojun HE ; Meidan YING
Acta Pharmaceutica Sinica B 2023;13(4):1522-1536
While neuroblastoma accounts for 15% of childhood tumor-related deaths, treatments against neuroblastoma remain scarce and mainly consist of cytotoxic chemotherapeutic drugs. Currently, maintenance therapy of differentiation induction is the standard of care for neuroblastoma patients in clinical, especially high-risk patients. However, differentiation therapy is not used as a first-line treatment for neuroblastoma due to low efficacy, unclear mechanism, and few drug options. Through compound library screening, we accidently found the potential differentiation-inducing effect of AKT inhibitor Hu7691. The protein kinase B (AKT) pathway is an important signaling pathway for regulating tumorigenesis and neural differentiation, yet the relation between the AKT pathway and neuroblastoma differentiation remains unclear. Here, we reveal the anti-proliferation and neurogenesis effect of Hu7691 on multiple neuroblastoma cell lines. Further evidence including neurites outgrowth, cell cycle arrest, and differentiation mRNA marker clarified the differentiation-inducing effect of Hu7691. Meanwhile, with the introduction of other AKT inhibitors, it is now clear that multiple AKT inhibitors can induce neuroblastoma differentiation. Furthermore, silencing AKT was found to have the effect of inducing neuroblastoma differentiation. Finally, confirmation of the therapeutic effects of Hu7691 is dependent on inducing differentiation in vivo, suggesting that Hu7691 is a potential molecule against neuroblastoma. Through this study, we not only define the key role of AKT in the progression of neuroblastoma differentiation but also provide potential drugs and key targets for the application of differentiation therapies for neuroblastoma clinically.