RESUMO
Ascofuranone, an isoprenoid antibiotic initially purified from a culture broth of Ascochyta viciae, has multiple anticancer effects. However, the impacts of ascofuranone on the epithelial-mesenchymal transition (EMT) and epidermal growth factor (EGF)-induced effects on human lung cancer cell lines have not been previously reported. Here, we show that ascofuranone exerts its anticancer effects by inhibiting the EGF-induced EMT and cell migration in human lung cancer cell lines. Ascofuranone significantly inhibited EGF-induced migration and invasion by lung cancer cells, and suppressed EGF-induced morphologic changes by regulating the expression of EMT-associated proteins. In addition, ascofuranone upregulated E-cadherin, and downregulated fibronectin, vimentin, Slug, Snail, and Twist. Inhibition of ERK/AKT/mTOR promoted EGF-induced E-cadherin downregulation and inhibited EGF-induced vimentin upregulation in response to ascofuranone, implying that inhibition of the EGF-induced EMT by ascofuranone was mediated by the ERK and AKT/mTOR pathways. Inhibition of c-Myc suppressed EGF-induced vimentin upregulation, suggesting the involvement of c-Myc. Collectively, these findings suggest that ascofuranone inhibits tumor growth by blocking the EGF-induced EMT through a regulatory mechanism involving ERK, AKT/mTOR, and c-Myc in lung cancer cells.
Assuntos
Antineoplásicos/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Sesquiterpenos/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Fator de Crescimento Epidérmico/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Neoplasias Pulmonares/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Cicatrização/efeitos dos fármacosRESUMO
BACKGROUND AND OBJECTIVES: To compare US-guided core-needle biopsy (USCNB) and US-guided fine-needle aspiration (USFNA) of suspicious cervical lymph nodes for staging workup of malignancies in locations other than the head and neck using propensity score matching (PSM). METHODS: This retrospective cohort study included 108 patients who underwent USFNA and 1058 who underwent USCNB for suspicious cervical lymph nodes detected by imaging modalities during the staging workup for malignancies located in regions other than the head and neck. The primary outcome was defined as the inconclusive results. To evaluate the procedures according to the outcome, we performed univariate and multivariate logistic regression analyses and a 1:1 PSM of USCNB and USFNA. RESULTS: There was no complication for both USFNA and USCNB. The inconclusive results were 6.5% (7/108) for USFNA and 1.6% (17/1058) for USCNB. A significantly lower rate of the inconclusive results in USCNB than in USFNA before matching was maintained after a 1:1 PSM of 103 patients from each group (before PSM, odds ratio (OR) = 4.489, 95% confidence interval (CI) [1.803-11.177], P = 0.001; after PSM, OR = 1.060, 95%CI [1.013-1.109], P = 0.012). CONCLUSIONS: Because USCNB can reduce inconclusive results compared to USFNA, it could be more helpful for staging workup of malignancies in locations other than the head and neck in patients with suspicious cervical lymph nodes.