Lung cancer is a major public health problem worldwide. Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer cases. Autophagy has recently sparked great interest, and it is thought to participate in a variety of diseases, including lung cancer. Uncoordinated (Unc) 51-like kinase 1 (Ulk1), a serine/threonine kinase, plays a central role in the autophagy pathway. However, the role of Ulk1 in NSCLC remains unclear. We report that NSCLC cell lines exhibited high expression of Ulk1 and that Ulk1 was negatively correlated with prognosis in lung cancer patients. Knockdown of Ulk1 or the inhibition of Ulk1 by the selective inhibitor SBI0206965, inhibited cell proliferation, induced cell apoptosis and enhanced the sensitivity of cisplatin against NSCLC cells. Moreover, we demonstrated that Ulk1 exerted oncogenic activity in NSCLC by modulating both autophagy and apoptosis pathways. Inhibition of autophagy by SBI0206965 sensitized NSCLC cells to cisplatin by inhibiting cisplatin induced cell-protective autophagy to promote apoptosis. Furthermore, SBI0206965 promoted apoptosis in NSCLC cells independent of autophagy, which was partly mediated by destabilization of Bcl2/Bclxl. In summary, our results show that inhibition of Ulk1 suppresses NSCLC cell growth and sensitizes NSCLC cells to cisplatin by modulating both autophagy and apoptosis pathways, and that Ulk1 might be a promising target for NSCLC treatment.

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The aim of the present study was to investigate the anti-cancer effects of the natural plant flavonoid, taxifolin, on human osteosarcoma cancer cells. Taxifolin was demonstrated to exhibit anti‑cancer effects on U2OS and Saos‑2 osteosarcoma cell lines. Treatment of cells with taxifolin inhibited proliferation and diminished colony formation in soft agar in a dose‑dependent manner. In vivo, intraperitoneal administration of taxifolin in nude mice bearing U2OS xenograft tumors, significantly inhibited tumor growth. In addition, taxifolin treatment was demonstrated to promote G1 cell cycle arrest and cell apoptosis in U2OS and Saos‑2 cell lines, as demonstrated by flow cytometry analysis. Western blot analysis demonstrated that taxifolin treatment was associated with a reduction in the expression levels of AKT serine/threonine kinase 1 (AKT), phosphorylated (p‑Ser473) AKT, v‑myc avian myelocytomatosis viral oncogene homolog (c‑myc) and S‑phase kinase associated protein 2 (SKP‑2) in U2OS and Saos‑2 cell lines. Overexpression of AKT considerably reversed the taxifolin‑induced decrease in AKT, c‑myc and SKP‑2 protein expression and the decrease in AKT phosphorylation, suggesting that inactivation of AKT was a mediator of taxifolin‑induced inhibition of c‑myc and SKP‑2. Furthermore, overexpression of SKP‑2 in U2OS cells partially reversed the growth inhibition mediated by taxifolin. Finally, taxifolin treatment repressed cell migration and invasion in U2OS cells and this effect was markedly reversed by SKP‑2 overexpression. The results of the present study indicate that taxifolin may present a potential novel therapeutic agent for osteosarcoma treatment.

BackgroundThe optimal surgical approach for treatment of multi-level cervical disc disease is currently widely debated. Anterior cervical discectomy and fusion (ACDF) combined with cervical disc arthroplasty (CDA) has been presented as a treatment approach, but to date, there are few reports with adequate clinical and radiological data for this hybrid surgical procedure. The goal of this paper is to assess clinical and radiological outcomes in patients with cervical spondylosis in three contiguous segments after treatment with artificial disc replacement combined with fusion.Materials and methodsWe performed a retrospective review of 36 patients (mean age of 48.6 years) with contiguous three-level cervical spondylosis who were treated with ACDF coupled with CDA (hybrid surgery) between October 2008 and October 2012. Clinical evaluation was based on the Neck Disability Index (NDI), Japanese Orthopaedic Association (JOA) score, and postoperative JOA score improvement rate (IR). Radiographic parameters, angular range of motion (ROM) for C2-C7, and ROM for the superior and inferior adjacent segments were measured before the operation, at 1, 3, 6, and 12 months postoperation, and at the final follow-up evaluation. All cases were followed for at least 28 months (range 28–65 months).ResultsAll patients exhibited significant postoperative improvement in NDI and JOA scores compared to preoperative levels (P < 0.05), and these improved scores were maintained during the follow-up period. The JOA score improvement rate was 70.83 % at the final follow-up evaluation. The mean C2-C7 ROM of all cases was significantly decreased immediately after operation but recovered to preoperative levels after 12 months (P = 0.721). The ROM of the superior and inferior adjacent segments was recovered to preoperative levels after 6 months (P > 0.05). One patient required a second surgery for symptomatic adjacent segment degeneration. Neither pseudarthrosis nor other device migration was observed in any patients during the entire follow-up period.ConclusionsThese results indicate that hybrid surgery seems to be a promising, acceptable, and alternative surgical approach for the treatment of multi-level cervical disc disease.