Honokiol suppresses proliferation and induces apoptosis via regulation of the miR­21/PTEN/PI3K/AKT signaling pathway in human osteosarcoma cells.

Honokiol (HNK) is a small biphenolic compound, which exerts antineoplastic effects in various types of cancer. However, the mechanism underlying the antitumor effects of HNK in osteosarcoma (OS) cells is not yet fully understood. Emerging evidence has indicated that microRNAs (miRNAs/miRs) serve key roles in numerous pathological processes, including cancer. It has previously been reported that Chinese medicinal herbs harbor anticancer properties via modulating miRNA expression. Therefore, the present study aimed to determine whether HNK could suppress OS cell growth by regulating miRNA expression. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometric analysis were used to evaluate the cell proliferation and apoptosis in human OS cells after treatment with HNK, respectively. The results demonstrated that HNK inhibits proliferation and induces apoptosis of human OS cells in a dose­dependent manner. Furthermore, HNK­induced apoptosis was characterized by upregulation of proapoptotic proteins, including cleaved­caspase­3, cleaved­poly (ADP­ribose) polymerase and B­cell lymphoma 2 (Bcl­2)­associated X protein, and downregulation of the anti­apoptotic protein Bcl­2. Reverse transcription­quantitative polymerase chain reaction (RT­qPCR) verified that HNK was able to induce aberrant expression of miRNAs in human OS cells, and miR­21 was one of the miRNAs that was most significantly downregulated. To further investigate miR­21 function, the present study validated that HNK reduces miR­21 levels in a dose­dependent manner. In addition, restoration of miR­21 expression abrogated the suppressive effects of HNK on OS cells. Luciferase assay and western blot analysis identified that miR­21 inhibits the expression of phosphatase and tensin homolog (PTEN) by directly targeting its 3'-UTR. Notably, HNK was able to suppress the phosphoinositide 3­kinase (PI3K)/protein kinase B (AKT) signaling pathway; however, it was reactivated by miR­21 overexpression. Taken together, these data indicated that HNK may inhibit proliferation and induce apoptosis of human OS cells by modulating the miR­21/PTEN/PI3K/AKT signaling pathway. Therefore, miR­21 may be considered a potential therapeutic target for the treatment of osteosarcoma with HNK.

miR-155 inhibitor reduces the proliferation and migration in osteosarcoma MG-63 cells.

As the most common malignant primary bone tumor in childhood, osteosarcoma (OS) maintains a high recurrence, despite the significant improvements in the overall survival rate of high-grade OS patients during the recent decades. Therefore, a novel therapy strategy is required for OS treatment. Recently, various microRNAs (miRNAs or miRs) have been confirmed as deregulated in OS, and the miR-155 dysregulation in OS has been discovered by the microarray analysis. In the present study, the regulation of miR-155 on the OS cell proliferation, migration and invasion on the MG-63 cells was explored in vitro. The miR-155 mimics were found to promote cell proliferation, colony formation, migration and invasion significantly, compared to the control miRNA. An miR-155 inhibitor was also used to evaluate whether miR-155 served as a therapeutic target for OS. The results demonstrated that the miR-155 inhibitor significantly reduced the proliferation, colony formation, migration and invasion of the MG-63 OS cells. Thus, the study confirmed the oncogenic regulation on the OS progression of miR-155, which could serve as a therapeutic target with an miR-155 inhibitor.

[An effect of the peripheral nerve allograft with subcutaneous preservation at different times on the nerve regeneration].

OBJECTIVE: To study an effect of the peripheral nerve allograft with subcutaneous preservation at different times on the sciatic nerve regeneration in rats. METHODS: Fifty-five Wistar rats were used in this experiment, which were randomly divided into the following 5 groups: the experimental groups (Groups A, B, C, 10 rats), the control group (Group D, 10 rats), and the donor group (Group E, 15 rats). In the experimental groups, a 15-mm segment of the sciatic nerve harvested from the donors was separately inserted into the subcutaneous compartment on the left thigh after the 1-week (Group A), 2-week (Group B), and 3-week (Group C) preservation; the segment of the sciatic nerve in the subcutaneous compartment was removed and transplanted into a 10-mm defect of the right sciatic nerve, which was made immediately. In Group D, a 10-mm sciatic nerve defect was made and immediately repaired in situ on the right thigh. The function of the sciatic nerve was evaluated by the sciatic functional index (SFI) at 2, 4, 6, 8, 10 and 12 weeks after operation. The histological and electrophysiological examinations were performed at 12 weeks after operation. RESULTS: After operation, SFI decreased gradually at 12 weeks after operation, SFI in Groups A and D was at the minimal level and had a significant difference compared with that in Groups B and C (P < 0.05). There was no significant difference between Group A and Group D. A large number of the myelinated nerve fibers and a small number of the unmyelinated nerve fibers were regenerated in Groups A and D. The number and the structure of the regenerated nerve were similar to the normal ones. The number and the size of the regenerated axon had a significant difference compared with those in Groups B and C (P < 0.05). There was no significant difference between Group A and Group D. The conduction velocity and the latent period of the motor nerve had significant differences between Groups A and D and Groups B and C (P < 0.05), and there was no significant difference between Group A and Group D. CONCLUSION: The nerve allograft with a 1-week subcutaneous preservation can promote nerve regeneration better.

[Advances in peripheral nerve allograft].

OBJECTIVE: To investigate the research advances of the peripheral nerve allograft. METHODS: The recent articles on peripheral nerve allograft were reviewed extensively. The treatments of allograft and host were analyzed. RESULTS: The immunogenicity of allograft was relieved by the physical, chemical or biological treatments; the immunosuppressive therapy makes the rejection relieved and the regeneration of axon accelerated. CONCLUSION: The effect of peripheral nerve allograft is inferior to autograft. If the immunologic tolerance are induced successfully, the problem shall be solved.