MiR-375 and Doxorubicin Co-delivered by Liposomes for Combination Therapy of Hepatocellular Carcinoma.

Doxorubicin (DOX) is one of the most frequently used anti-cancer drugs and the front line option for hepatocellular carcinoma (HCC) treatment. However, the clinical applications of DOX are restricted largely due to its toxicity and chemoresistance. Here, we report that miR-375 and DOX were co-delivered by liposomes (named L-miR-375/DOX-NPs) for combination therapy of HCC and drug resistance reversion of DOX. In vitro, L-miR-375/DOX-NPs could deliver DOX and miR-375 efficiently and simultaneously into HCC cells and ensure the successful release of mature miR-375 and DOX. Then, the released miR-375 suppressed the malignant hallmarks of HCC by significantly decreasing the expression of AEG-1, YAP1, and ATG7, while the released DOX evidently accelerated cell apoptosis and blocked cycle at a G2/M stage by activating the P53/Bax/Bcl-2, caspase-3, and P-JNK, P-P38 pathway. Furthermore, miR-375 dramatically inhibited drug resistance of DOX by reducing the expression of multidrug resistance gene 1 (MDR1). In vivo, L-miR-375/DOX-NPs exhibited enhanced anti-tumor efficiency in xenograft HCC mouse models with mild adverse effects compared with doxorubicin or miR-375 alone. In conclusion, our research demonstrated that L-miR-375/DOX-NPs had significant synergetic anti-tumor effects and added values in overcoming drug resistance, which may represent a promising approach for the therapy of HCC.

MiR-101 and doxorubicin codelivered by liposomes suppressing malignant properties of hepatocellular carcinoma.

MiR-101, an important tumor-suppressive microRNA (miRNA) in hepatocellular carcinoma (HCC), has been affirmed significantly downregulated in HCC and participated in promoting apoptosis, decreasing proliferation and invasiveness of HCC cells, as well as increasing sensitivity of chemotherapeutic drug. However, miR-101-based combination therapies with doxorubicin (DOX) are not reported yet. Recently, nanomaterials-based approaches, especially liposome formulations, have been approved for clinical use and seem to provide a great opportunity to codeliver therapeutic agents for cancer therapy. In this study, we have successfully prepared liposome (L) nanoparticles to efficiently deliver miR-101 and DOX to HCC cells simultaneously. The effects of codelivery system miR-101/doxorubicin liposome (miR-101/DOX-L) on tumor malignant phenotypes of HCC cells were evaluated through analyzing cell proliferation, colony formation, cell migration, cell invasion, cell apoptosis assay, and the expression of related genes. In subcutaneous xenografts developed by HCC cells, the inhibition of tumor growth was analyzed through gross morphology, growth curve, proliferation marker Ki-67, apoptosis signals, and the expression of related genes. These experiments demonstrated that miR-101/DOX-L inhibited tumor properties of liver cancer cells in vitro and in vivo through targeting correlative genes by combinatory role of miR-101 and DOX. In conclusion, our results indicated that liposome nanoparticle is a reliable delivery strategy to codeliver miR-101 and DOX simultaneously, and miR-101- and DOX-based combination therapy can result in significant synergetic antitumor effects in vivo and vitro.

The experimental study on effect of the spinal neuron flow with the nerve repair time / 中华显微外科杂志

Objective To measure Ihe effect on rats spinal neuron flow according nerve roots repair time.Methods We adopted the experimental rats on the root avulsion and extravertebral foramen nerve root divison of C_(5～7).We divided them into four groupsin each which there were 16 ratsaccording the type of nerves root injury and repair timeGroup AC:the avulsed roots were reimplanted into the spinal cord and the transeeted roots were sutured to the proximal stump immediately.Group B,Dthe avulsed roots and the transected roots were reimplanted into the spinal cord or were sutured to the proximal stump in delayed 3 weeks each with 16 rats.At the different time point(3 weeks3 months6 months)through pathological examina- tion and immunohistological lechniques and nerve tracing techniqueswe examined the spinal cord and distal nerve trunk in order to observe the pathologic changes and axonal regeneration.Results Group A、C were much better than group B、D in the numberthe conformation and the degree of abatement of spinal motoneu- rons and nissl body.It is the same on the number and the development level of regenerating nerve fiber. Conclusion It had the advantage of neuronal protection and nerve regeneration that reparing the injured nerve roots earlv after nerve roots injury.