ABSTRACT
BACKGROUND: Oesophageal adenocarcinoma (EAC) is a highly lethal cancer associated with a rapidly rising incidence and a poor prognosis. Alantolactone, a sesquiterpene lactone isolated from inula helenium, has anti-inflammatory, antimicrobial, neuroprotective activities, and anticancer properties. OBJECTIVE: In the present study, the anticancer effects of alantolactone on the human EAC cells were investigated in vitro and in vivo. METHODS AND FINDINGS: After treated with alantolactone, the cell viability of KYAE-1, KYAE-2, OE19, and OE33 cells reduced significantly compared with that of the control cells. Alantolactone induced apoptosis of the EAC cell lines by inhibiting the protein expression levels of nuclear factor erythroid2-related factor 2 (Nrf2). Furthermore, the apoptosis-inducing effect of alantolactone was enhanced by Nrf2 knockdown while reduced by overexpression of Nrf2. Antioxidant α-tocopherol and glutathione can protect EAC cell lines against alantolactone. A xenograft nude mice model showed that alantolactone can inhibit EAC growth in vivo. CONCLUSIONS: Alantolactone inhibits oesophageal adenocarcinoma cells through Nrf2-mediated reactive oxygen species (ROS) increment. Alantolactone maybe a potential therapeutical candidate for treating EAC.
Subject(s)
Adenocarcinoma , Esophageal Neoplasms , Reactive Oxygen Species , Sesquiterpenes, Eudesmane , Animals , Humans , Mice , Adenocarcinoma/drug therapy , Apoptosis , Cell Line, Tumor , Lactones/pharmacology , Mice, Nude , NF-E2-Related Factor 2/drug effects , NF-E2-Related Factor 2/metabolism , Reactive Oxygen Species/metabolism , Sesquiterpenes, Eudesmane/pharmacology , Esophageal Neoplasms/drug therapyABSTRACT
Purpose: To develop and validate a quantitative model based on gross tumor volume (GTV) of gastric adenocarcinoma (GA) corresponding to N-stage measured at multidetector computed tomography (CT) for preoperative determination of resectability. Materials and methods: 493 consecutive patients with confirmed GA undergoing contrast-enhanced CT two weeks before treatments were randomly enrolled into the training cohort (TC, n = 271), internal validation cohort (IVC, n = 107) and external validation cohort (EVC, n = 115). GTV was measured on CT by multiplying sums of all tumor areas by section thickness. In TC, univariate and multivariate analyses were performed to select factors associated with resectability. Receiver operating characteristic (ROC) analysis was to determine if N-stage based GTV could identify resectability. In IVC and EVC, unweighted Cohen's Kappa tests were to evaluate performances of the ROC models. Results: According to univariate analysis, age, cT stage, cN stage and GTV were related to resectability in TC (all P-values < 0.05), and multivariate analysis suggested that cN stage and GTV were independent risk factors with odds ratios of 1.594 (95% confidence interval [CI]: 1.105-2.301) and 1.055 (95%CI: 1.035-1.076), respectively. ROC analysis in TC revealed the cutoffs of 21.81, 21.70 and 36.93 cm3 to differentiate between resectable and unresectable cancers in stages cN0-3, cN2 and cN3 with areas under the curves of more than 0.8, respectively, which was validated in IVC and EVC with average Cohen k-values of more than 0.72. Conclusions: GTV and cN stage can be independent risk factors of unresectable GA, and N-stage based GTV can help determine resectability.
