The NF-kappa B inhibitor, celastrol, could enhance the anti-cancer effect of gambogic acid on oral squamous cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Gambogic acid (GA) is a major active ingredient of gamboge, a widely used traditional Chinese medicine that has been reported to be a potent cytotoxic agent against some malignant tumors. Many studies have shown that the NF-kappa B signaling pathway plays an important role in anti-apoptosis and the drug resistance of tumor cells during chemotherapy. In this study, the effects and mechanisms of GA and the NF-kappa B inhibitor celastrol on oral cancer cells were investigated.</p> <p>Methods</p> <p>Three human oral squamous cell carcinoma cell lines, Tca8113, TSCC and NT, were treated with GA alone, celastrol alone or GA plus celastrol. Cytotoxicity was assessed by MTT assay. The rate of apoptosis was examined with annexin V/PI staining as well as transmission electronic microscopy in Tca8113 cells. The level of constitutive NF-kappa B activity in oral squamous cell carcinoma cell lines was determined by immunofluorescence assays and nuclear extracts and electrophoretic mobility shift assays (EMSAs) <it>in vitro</it>. To further investigate the role of NF-kappa B activity in GA and celastrol treatment in oral squamous cell carcinoma, we used the dominant negative mutant SR-IκBα to inhibit NF-kappa B activity and to observe its influence on the effect of GA.</p> <p>Results</p> <p>The results showed that GA could inhibit the proliferation and induce the apoptosis of the oral squamous cell carcinoma cell lines and that the NF-kappa B pathway was simultaneously activated by GA treatment. The minimal cytotoxic dose of celastrol was able to effectively suppress the GA-induced NF-kappa B pathway activation. Following the combined treatment with GA and the minimal cytotoxic dose of celastrol or the dominant negative mutant SR-IκBα, proliferation was significantly inhibited, and the apoptotic rate of Tca8113 cells was significantly increased.</p> <p>Conclusion</p> <p>The combination of GA and celastrol has a synergistic antitumor effect. The effect can be primarily attributed to apoptosis induced by a decrease in NF-kappa B pathway activation. The NF-kappa B signaling pathway plays an important role in this process. Therefore, combining GA and celastrol may be a promising modality for treating oral squamous cell carcinoma.</p

Progress of translational research on biomarker⁃based oral squamous cell carcinoma treatment

A biomarker is defined as a biological molecule found in the blood, other body fluids, or tissues that is a sign of normal or abnormal processes or a condition or disease. In cancer research, biomarkers are classified as diagnos⁃ tic, prognostic, or predictive. The identification and application of biomarkers in clinical practice are important for eval⁃ uating their usefulness for clinical diagnosis, treatment and prognostic warning and for determining the biological effects of anti⁃cancer drugs, and they are currently one of the hottest topics in oncological translational research. Currently, translational research on biomarkers mostly focus on oncological diagnosis and molecular typing, targeted therapy, treat⁃ ment protocol selection and optimization, prognostic prediction, etc. Here, we review the progress of translational re⁃ search on treatments based on biomarkers in oral squamous cell carcinoma as well as the clinical application of inhibi⁃ tors targeting EGFR, PD1, PI3K, WEE1, the Wnt/β ⁃catenin pathway, the SHH pathway, and the ERK pathway. The prospect of research strategies for personalized treatments based on biomarkers in oral squamous cell carcinoma is also discussed

A New Oviraptorosaur (Dinosauria: Oviraptorosauria) from the Late Cretaceous of Southern China and Its Paleoecological Implications

<div><p>A new oviraptorosaur <i>Nankangia jiangxiensis</i> gen. et sp. nov. is described on the basis of a partial postcranial skeleton with a partial lower jaw collected from the Upper Cretaceous Nanxiong Formation of Ganzhou, in Jiangxi Province of southern China. The new taxon is diagnosed by: (1) a mandibular symphysis that is not turned down; (2) neural spines of the cranial caudal vertebrae that are wider transversely than anteroposteriorly, forming a large posterior fossa with rugose central areas; (3) a femoral neck extending at an angle of about 90 to the shaft; and (4) a ratio of femur to tibia length of 0.95. Phylogenetic analysis recovers <i>Nankangia</i> as basal to the oviraptorid <i>Yulong</i>, but more derived than <i>Caenagnathus</i>, which also has a mandibular symphysis that is not turned down. The coexistence of <i>Nankangia jiangxiensis</i>, <i>Ganzhousaurus nankangensis, Jiangxisaurus ganzhouensis</i>, an unnamed oviraptorid from Nanxiong Basin and <i>Banji long</i> suggests that they occupied distinct ecological niches. <i>Nankangia</i> may have been more herbivorous than carnivorous.</p></div

Pelvic girdle of <i>Nankangia</i> (GMNH F10003).

<p><b>A</b>, Partial left pelvis (missing dorsal edge of ilium and most of pubis) in lateral view. <b>B</b>, Partial right pelvis (missing pubis) in lateral view. <b>C</b>, Pubes in left lateral view. Abbreviations: dv., dorsal vertebrae; ili., ilium; isc., ischium; pub., pubis. Scale bar  = 5 cm.</p

Femur, tibia, and proximal tarsals of <i>Nankangia</i> (GMNH F10003).

<p><b>A</b>, Left femur in posterior view; <b>B</b>, Right femur in posterior view; <b>C</b>, Close up of the distal portion of the right femur in posterior view, showing the pathological area; <b>D</b>, Right femur and tibia in anterior view; <b>E</b>, Close-up of the distal portion of the tibia, the astragalus, and the calcaneum in anterior view; <b>F</b>, Left femur in lateral view. Abbreviations: ap., ascending process of astragalus; cal., calcaneum; f1–f3, fossae 1–3; path., pathological areas. Scale bar  = 1 cm in <b>C</b>; 5 cm in other images.</p

Comparisons of lower jaws (anterior ends) of some oviraptorosaurs.

<p><b>A</b>, <i>Caudipteryx</i> sp. (IVPP 12430, modified from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0080557#pone.0080557-Zhou1" target="_blank">[14]</a>) (reversed); <b>B</b>, <i>Yulong mini</i> (HGM 41HIII-0109); <b>C</b>, <i>Khaan mckennai</i> (IGM 100/973, modified from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0080557#pone.0080557-Balanoff1" target="_blank">[12]</a>); <b>D</b>, <i>Nemegtomaia barsboldi</i> (GIN100/2112); <b>E</b>, <i>Incisivosaurus gauthieri</i> (IVPP V13326); <b>F</b>, <i>Chirostenotes pergracilis</i> (CMN 8776: <i>Caenagnathus collinsi</i>, from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0080557#pone.0080557-Currie2" target="_blank">[27]</a>; reversed); <b>G</b>, “<i>Caenagnathus</i> cf. <i>sternbergi</i>” (RTMP 92.36.390, from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0080557#pone.0080557-Currie2" target="_blank">[27]</a>). <b>H</b>, <i>Nankangia jiangxiensis</i> gen. nov. (GMNH F10003). Scale bars  = 1 cm.</p

Comparison of ilia among selected oviraptorosaurs in right lateral view.

<p><b>A</b>, Left ilium of <i>Caudipteryx dongi</i> (reversed); <b>B</b>, Left ilium of <i>Chirostenotes pergracilis</i> (reversed); <b>C</b>, Right ilium of <i>Ingenia yanshini</i>; <b>D</b>, Right ilium of <i>Rinchenia mongoliensis</i>; <b>E</b>, Right ilium of <i>Heyuannia huangi</i>; <b>F</b>, Right ilium of <i>Nemegtomaia barsboldi</i>; <b>G</b>, Left ilium of <i>Nomingia gobiensis</i> (reversed); <b>H</b>, Left ilium of <i>Shixinggia oblita</i> (reversed); <b>I</b>, Left ilium of <i>Luoyanggia liudianensis</i> (reversed); <b>J</b>, Right ilium of <i>Nankangia jiangxiensis</i> gen. et sp. nov. <b>A</b>–<b>H</b> are modified from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0080557#pone.0080557-L5" target="_blank">[17]</a>, <b>I</b> is from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0080557#pone.0080557-L6" target="_blank">[21]</a>. No scale.</p

Scapulocoracoids of <i>Nankangia</i> (GMNH F10003) in lateral (right scapulocoracoid) and medial (left scapulocoracoid) views.

<p>Abbreviations: acr., acromion of the scapula; cf., coracoid foramen; cr., coracoid; hlpp., horn-like posteroventral process; lsc., left scapula; rsc., right scapula. Scale bar  = 5 cm.</p

Strict consensus of two most parsimonious trees obtained by PAUP, based on analysis of 20 taxa and 182 characters [31].

<p>Each tree has a length of 370 and was recovered via a branch and bound search (CI = 0.58, HI = 0.42, RI = 0.69).</p