dendrobine and Carcinoma--Non-Small-Cell-Lung

Non-small cell lung cancer (NSCLC) accounts for about 80% of lung cancers. Cisplatin is a broad-spectrum anti-cancer drug and is often used in combination with other drugs. Research suggests that dendrobine, a pyrrolizidine derivative alkaloid, exhibits antitumor activity in various cancers. This study explores the effect of dendrobine combined with cisplatin on NSCLC and its underlying molecular mechanism.. The effects of dendrobine combined with cisplatin on tumor progression were evaluated by xenograft model (in vivo) and clonogenic survival assay (in vitro) using H1299 cell line. Annexin V staining was used for detecting apoptotic cells. The population of T cells, B cells and other subpopulations in the peripheral blood was determined by flow cytometry.. Dendrobine combined with cisplatin prolonged the survival of mice implanted with H1299 cells and reduced tumor volume compared with single drug application. However, dendrobine exhibited no effect on H1299 cells in clonal survival assays with or without cisplatin treatment and did not promote cisplatin-induced apoptosis in vitro. Importantly, dendrobine suppressed the regulatory T cells (Treg cells) and enhanced the T helper 17 cells (Th17 cells). Treatment of dendrobine significantly reduced Foxp3, and increased the level of IL-17 in serum.. Dendrobine displayed a synergistic effect with cisplatin to exert anti-tumor effect in vivo, which might be achieved by modulating the balance of Treg/Th17 cells rather than regulating cell apoptosis.

Topics: Animals; Apoptosis; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cisplatin; Humans; Lung Neoplasms; Mice; T-Lymphocytes, Regulatory; Th17 Cells

Lung cancer is a leading cause of cancer-related death worldwide. Cisplatin-based chemotherapy is the standard treatment for lung cancer, but chemoresistance and adverse effects especially cardiotoxicity limit its efficacy.. The efficacy of combination treatment of dendrobine, a plant alkaloid isolated from Dendrobium nobile, with cisplatin was examined as a possible anti-non-small cell lung cancer strategy.. The cytotoxicity of dendrobine and cisplatin against A549 lung cancer cells was analyzed by MTT and colony formation assays. Apoptosis was measured by annexin V/PI double staining. Apoptosis-related proteins were assessed by western blotting and qPCR analysis. In vivo efficacy was determined using A549 xenograft in nude mice. JNK and Bim inhibition were achieved by siRNA knockdown and/or chemical inhibition. Cardiotoxicity was assessed by serum creatine phosphokinase activity assay.. Dendrobine induced apoptotic cell death through mitochondrial-mediated pathway. Combination treatment of dendrobine with cisplatin showed enhanced cytotoxicity through stimulation of JNK/p38 stress signaling pathways and, consequently, the induction of apoptosis involving pro-apoptotic proteins Bax and Bim. In addition, dendrobine attenuated the body weight reduction and cardiotoxicity induced by cisplatin in nude mice.. The combination treatment showed enhanced anticancer activity toward non-small cell lung cancer cells without aggravating the cardiotoxic effects of cisplatin suggesting that the combination strategy deserves further investigation for human lung cancer treatment.

Topics: A549 Cells; Alkaloids; Animals; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Apoptosis Regulatory Proteins; Body Weight; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cisplatin; Female; Humans; Lung Neoplasms; MAP Kinase Signaling System; Mice, Inbred BALB C; Mitochondria; Xenograft Model Antitumor Assays