Plumbagin shows anticancer activity in human osteosarcoma (MG-63) cells via the inhibition of S-Phase checkpoints and down-regulation of c-myc.

OBJECTIVE: Plumbagin, a naphthoquinone constituent of Plumbago zeylanica L. (Plumbaginaceae), has been extensively studied for its pharmacological activities and reported to show a good anti-cancer activity in different human cancer cell lines. It is known to exhibit proapoptotic, antiangiogenic and antimetastatic effects in cancer cells. Plumbagin is also known to inhibit NF-κB, JNK (Hsu), PKCε, and STAT-3. However, the anti-proliferatory activity and their core molecular mechanisms have been poorly determined. METHODS: Human osteosarcoma (MG-63) cells were exposed to plumbagin and the anti-proliferative activity was evaluated by MTT assay. The mechanism of action for the growth inhibitory activity of plumbagin on MG-63 cells was evaluated using flow cytometry for cell cycle distribution, and western blot for assessment of accumulation and phosphorylation of potential target proteins. Furthermore, morphology of MG-63 cells was assessed after treatment with Plumbagin. RESULTS: Plumbagin has significantly induced growth inhibition against osteosarcoma MG-63 cells, primarily by S-phase cell cycle arrest which is confirmed by the down regulation of cyclin A and CDK2 protein levels determined by western blot analysis. It was also found that plumbagin has triggered the DNA damage in MG-63 cells, subsequently initiating the arrest in S-phase, which is evident by the up-regulation of phosphorylated p53 and histone. Furthermore, plumbagin resulted in the down-regulation of c-myc protein expression in the MG-63 cells. CONCLUSION: Plumbagin has triggered DNA damage and had induced S-phase arrest in MG-63 cells, suggesting it to be a potential compound in treatment against malignant human osteosarcoma.

miRNA expression profile during osteogenic differentiation of human adipose-derived stem cells.

Human adipose-derived stem cells (hADSC) are capable of differentiating into an osteogenic lineage. It is believed that microRNAs (miRNAs) play important roles in regulating this osteogenic differentiation of human adipose-derived cells, although its molecular mechanism remains unclear. We investigated the miRNA expression profile during osteogenic differentiation of hADSCs, and assessed the roles of involved miRNAs during the osteogenic differentiation. We obtained and cultured human adipose-derived stems cells from donors who underwent elective liposuction or other abdominal surgery at our institution. miRNA expression profiles pre- and post-osteogenic induction were obtained using microarray essay, and differently expressed miRNAs were verified using quantitative real-time polymerase chain reaction (qRT-PCR). The expression of osteogenic proteins was detected using an enzyme-linked immunosorbent assay. Putative targets of the miRNAs were predicted using online software MiRanda, TargetScan, and miRBase. Eight miRNAs were found differently expressed pre- and post-osteogenic induction, among which four miRNAs (miR-17, miR-20a, miR-20b, and miR-106a) were up-regulated and four miRNAs (miR-31, miR-125a-5p, miR-125b, and miR-193a) were down-regulated. qRT-PCR analysis further confirmed the results. Predicted target genes of the differentially expressed miRNAs based on the overlap from three public prediction algorithms: MiRanda, TargetScan, and miRBase Target have the known functions of regulating stem cell osteogenic differentiation, self-renewal, signal transduction, and cell cycle control. We identified a group of miRNAs that may play important roles in regulating hADSC cell differentiation toward an osteoblast lineage. Further study of these miRNAs may elucidate the mechanism of hADSC differentiation into adipose tissue, and thus provide basis for tissue engineering.

[Application of lumbar-pelvic fixation in lumbosacral reconstruction after resection of sacral tumors].

OBJECTIVE: To evaluate the short-term clinical results of a new approach of lumbar-pelvic fixation for lumbosacral reconstruction after resection of sacral tumors. METHODS: Fifteen patients with sacral tumors underwent lumbar-pelvic fixation using TSRH-3D, CDH-M8 or ISOLA with iliac screws. The lumbosacral stability was evaluated according to the X-ray result to assess the feasibility and therapeutic effect of this approach. RESULTS: X-ray showed that high lumbosacral stability was achieved in all the 15 cases after the operation, and satisfactory therapeutic effect was obtained. CONCLUSION: Lumbar-pelvic fixation with iliac screw is feasible for lumbosacral reconstruction after resection of the sacral tumors, which provides strong internal fixation and produce good clinical outcomes.

[Comparison of surgical treatment in single thoracolumbar-lumbar adolescent idiopathic scoliosis: anterior versus posterior surgery].

OBJECTIVE: To retrospectively compare the clinical outcomes of anterior and posterior surgical treatment in single thoracolumbar-lumbar adolescent idiopathic scoliosis. METHODS: Between January 2004 and August 2008, 22 female patients, averaged 14.5 years old (12 to 18 years), of thoracolumbar-lumbar adolescent idiopathic scoliosis were corrected by anterior correction and fusion. At the same time, 20 female patients, average 14.8 years old (11 to 19 years), were corrected by posterior segmental pedicle screw correction and fusion. Operation time, SRS-24 score, intraoperative blood loss, and coronal and sagittal plane correction were compared between the two groups. RESULTS: All patients were followed up for 12 to 63 months, the mean follow-up time was 28.3 months. Operation time was (334 + or - 36) min in anterior group and (292 + or - 17) min in posterior group; intraoperative blood loose was (940 + or - 207) ml in anterior group and (596 + or - 227) ml in posterior group; fusion levels were (5.2 + or - 0.8) in anterior group and (6.7 + or - 1.2) in posterior group. There were statistically significant difference in operation time, intraoperative blood loss and fusion levels (P < 0.05). Coronal correction was (93 + or - 5)% in anterior group and (88 + or - 5)% in posterior group. SRS-24 scores averaged 98 in anterior group and averaged 94 in posterior group. There was no statistical difference in coronal correction or SRS-24 scores (P > 0.05). CONCLUSIONS: Posterior surgery has the same correction results compared with anterior surgery in treating thoracolumbar-lumbar adolescent idiopathic scoliosis. Posterior surgery takes less operation time, brings less trauma but has longer fusion levels.