Abstract
:Overexpression of Bmi1 gene is an important feature of cancer stem cell in various human tumors. Therefore, Bmi1 gene can be a potential target for small interfering RNA (siRNA) mediated cancer therapy. Ursolic acid (UA) as a natural product plays a pivotal role in anti-tumor field, although its performance is limited by low bioavailability and poor hydrophilicity. A folate receptor-targeted cationic liposome system was designed for the purpose of investigating the relationship between Bmil siRNA and UA. The folate receptor-targeted cationic liposomes co-delivering UA and Bmi1 siRNA (FA-UA/siRNA-L) were fabricated by electrostatic interaction between folate UA liposome (FA-UA-L) and Bmi1 siRNA. Tumor growth is inhibited by FA-UA/siRNA-L in vitro and in vivo and this inhibition is contributed by a synergistic anti-tumor effect of UA and Bmi1 siRNA. The western blot measurement of apoptosis-protein and cancer stem cell (CSC) marked-protein demonstrated that UA led to activation-induced tumor cell death and Bmi1 siRNA resulted in inhibition of cancer stem cells. Overall, these results indicate that Bmi1 as a regulating gene for cancer stem cell is an effective target for cancer treatment using siRNA and co-delivery of UA and Bmi1 siRNA using folate-targeted liposomes is a promising strategy for improved anti-tumor effect.
Highlights
It is widely acknowledged that small interfering RNA plays a key role in gene therapy and can be potentially applied in clinical practice
After Bmi1 small interfering RNA (siRNA) was absorbed on the surface of liposomes, the average particle sizes were increased to 162.7 for Ursolic acid (UA)/siRNA-L and 165.1 nm for FA-UA/ siRNA-L
The absorption of Bmi1 siRNA reduced the zeta potential of UA/siRNA-L and FA-UA/siRNA-L to 21.3 and 18.6 mV respectively. This is owing to that the positive charge of liposome was partly neutralized by negative charge Bmi1 siRNA
Summary
It is widely acknowledged that small interfering RNA (siRNA) plays a key role in gene therapy and can be potentially applied in clinical practice. Several recent studies on cancer stem cells have shown that down-regulation of Bmi could inhibit the tumor cell growth in different types of cancer, indicating that Bmi can be a potential target for tumor treatment (Liang et al, 2013; Zhu et al, 2014). The molecular mechanism of using siRNA to down-regulate Bmi expression has been reported (Gargiulo et al, 2013), the biological applicability and clinical translation of Bmi siRNA based therapy are still limited. This is mainly because siRNA showed poor internalization into tumor cells, fast systemic clearance and was susceptible to enzymatic degradation (Hahn et al, 2004; Hoerter et al, 2011)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
