Shikonin inhibits tumor invasion via down-regulation of NF-κB-mediated MMP-9 expression in human ACC-M cells.

OBJECTIVE: The aim of this study was to examine the anti-invasion effect of Shikonin on human high-metastatic adenoid cystic carcinoma (ACC-M) cells and to explain the possible molecular mechanism involved. METHODS: The ACC-M cells were treated with Shikonin (0, 2.5, 5, 10 µM) for 24 h. The protein levels and gelatinolytic activities of MMP-2 and MMP-9 were analyzed using Western blot and Gelatin zymography test, respectively. Matrigel invasion assays were used to investigate tumor invasive potential and electromobility shift assays were used to determine the activity of NF-κB. RESULTS: The invasiveness of ACC-M cells was reduced in a dose dependent manner following 24-h treatment of up to 10 µM of the Shikonin at which concentration no cytotoxicity occurred. The protein levels and gelatinolytic activities of MMP-9 were significantly suppressed by increasing Shikonin concentrations. The down-regulation of MMP-9 appeared to be via the inactivation of NF-κB as the treatment with Shikonin suppressed the protein level of phosphate-IkBa, which was accompanied by a decrease in DNA-binding level of the factor. CONCLUSIONS: Shikonin inhibits tumor invasion via downregulation of MMP-9 expression in ACC-M cells. Pharmacologic inhibition of the NF-κB-mediated MMP-9 expression by Shikonin might be a powerful treatment option for ACC patients in future.

Swallow recovery in an oral cancer patient following surgery, radiotherapy, and hyperthermia.

BACKGROUND: No study has examined the nature and extent of swallowing impairment in oral cancer patients following treatment with combined hyperthermia and interstitial radiotherapy. Few studies have examined the effects of voluntary swallow maneuvers (supersupraglottic and Mendelsohn) on pharyngeal phase swallowing in the oral cancer patient treated with surgery or radiotherapy. This study examined the effects of combined radiotherapeutic salvage treatments of hyperthermia and interstitial implantation and swallow recovery using swallow maneuvers in a surgically treated and irradiated oral cancer patient. METHODS: The patient under study, a 51-year-old man, underwent radiotherapy, according to Radiation Therapy Oncology Group (RTOG) protocol #8419, consisting of a combination of interstitial irradiation and hyperthermia to the base of tongue, for a recurrent squamous cell cancer. He underwent videofluorographic (VFG) examination of his swallowing, a modified barium swallow at three time points: 2 days following radiotherapy treatment (VFG1), 4 weeks later (VFG2), and 8 months later (VFG3). Temporal and biomechanical analyses of swallows were performed at each time point. RESULTS: Swallow maneuvers and time resulted in improved laryngeal elevation and laryngeal vestibule closure during the swallows on VFG2. Maximum upper esophageal sphincter (UES) opening width and duration were more normal. Fewer swallows were required for bolus clearance through the pharynx. Base of tongue tissue necrosis occurred as a complication of radiotherapy between VFG2 and VFG3, with resultant severe reduction in posterior movement of the tongue base, incomplete tongue base contact to the posterior pharyngeal wall, reduced laryngeal elevation, and incomplete laryngeal vestibule closure during swallowing at VFG3. UES opening became less normal and a greater number of swallows were required for bolus clearance through the pharynx. CONCLUSIONS: Combined interstitial irradiation and hyperthermia can cause oropharyngeal swallowing problems. Time and swallow therapy can improve these swallow disorders. Tongue base tissue necrosis can cause further swallow impairment, emphasizing the importance of the tongue base in normal deglutition. Further studies are needed to examine the impact of combined hyperthermia and interstitial implantation for treatment of tongue base tumors on swallow functioning in a larger group of patients.