Although carboplatin is one of the standard chemotherapeutic agents for non-small cell lung cancer (NSCLC), it has limited therapeutic efficacy due to activation of a survival signaling pathway and the induction of multidrug resistance. Curcumin, a natural compound isolated from the plant Curcuma longa, is known to sensitize tumors to different chemotherapeutic agents. The aim of this study is to evaluate whether curcumin can chemosensitize lung cancer cells to carboplatin and to analyze the signaling pathway underlying this synergism. We investigated the synergistic effect of both agents on cell proliferation, apoptosis, invasion, migration, and expression of related signaling proteins using the human NSCLC cell line, A549. A549 cell was treated with different concentrations of curcumin and carboplatin alone and in combination. Combined treatment with curcumin and carboplatin inhibited tumor cell growth, migration, and invasion compared with either drug alone. Matrix metalloproteinase (MMP)-2 and MMP-9 were more efficiently downregulated by co-treatment than by each treatment alone. mRNA and protein expression of caspase-3 and caspase-9 and proapoptotic genes was increased in cells treated with a combination of curcumin and carboplatin, whereas expression of the antiapoptotic Bcl-2 gene was suppressed. Co-treatment of both agents substantially suppressed NF-kB activation and increased expression of p53. Phosphorylation of Akt, a protein upstream of NF-kB, was reduced, resulting in inhibition of the degradation of inhibitor of kB(IkBa), whereas the activity of extracellular signal-regulated kinase (ERK1/2) was enhanced. Our study demonstrated that the synergistic antitumor activity of curcumin combined with carboplatin is mediated by multiple mechanisms involving suppression of NF-kB via inhibition of the Akt/IKKa pathway and enhanced ERK1/2 activity. Based on this mechanism, curcumin has potential as a chemosensitizer for carboplatin in the treatment of patients with NSCLC.
An 81-year-old man underwent bronchoscopy to investigate the cause of his dyspnea symptoms. A benign natured mass was observed in the bronchus and was excised. The pathology examination revealed a fibroepithelial polyp. He has been asymptomatic since the simple bronchoscopic excision.A fibroepithelial polyp is a benign tumor with a mesodermal origin. It is commonly found in the skin, urogenital area and chest, but is extremely rare in the respiratory system. We report a case of a fibroepithelial polyp in the bronchus, which was treated with a bronchoscopic excision, with a brief review of the relevant literature. Tuberc Respir Dis 2005; 59:670-673)
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