Enhancing effect of connexin 32 gene on vinorelbine-induced cytotoxicity in A549 lung adenocarcinoma cells. 2007

Hiromi Sato, and Keiko Fukumoto, and Sachio Hada, and Hiromi Hagiwara, and Eriko Fujimoto, and Etsuko Negishi, and Koichi Ueno, and Tomohiro Yano
Project for Complementary Factors, National Institute of Health and Nutrition, 1-23-1 Toyama, Tokyo 162-8636, Japan.

OBJECTIVE Connexin (Cx) genes exert negative growth effects on tumor cells with certain cell specificity, and tumor-suppressive effects of the Cx genes contribute to enhancement of chemotherapeutical agents-induced cytotoxicity in some cancer cells. Since we and others have been reported that Cx32 acts as a tumor suppressor gene in lung adenocarcinomas, this study was undertaken to estimate if the combination of Cx32-dependent tumor-suppressive effect and vinorelbine (VBN), a chemotherapeutic agent which has been utilized for clinical lung adenocarcinoma treatment, could be effective in enhancing the sensitivity of the lung cancer to VBN treatment. METHODS We established the A549 cells (a human lung adenocarcinoma cell line) which had stable expression of Cx32 and estimated effect of Cx32 on VBN-induced cytotoxicity in the established cells. RESULTS Cx32 expression in A549 cells significantly potentiated VBN-induced cytotoxicity on the cells due to enhancement of apoptosis induction. The enhancing cytotoxicity in A549 cells by Cx32 mainly depended on a decrease in expression of multi-drug resistance-1 (MDR-1) gene responsible for reduction of VBN accumulation into the cells. We also observed that silencing of Cx32 by siRNA treatment elevated the expression level of MDR-1 mRNA in A549 cells and that inhibition of MDR-1 gene product-dependent function enhanced VBN-induced cytotoxicity in the cells. CONCLUSIONS These results suggest that Cx32 contributes to the enhancement of VBN-induced cytotoxicity in A549 cells via the reduction of MDR-1 expression.

UI MeSH Term Description Entries
D008175 Lung Neoplasms Tumors or cancer of the LUNG. Cancer of Lung,Lung Cancer,Pulmonary Cancer,Pulmonary Neoplasms,Cancer of the Lung,Neoplasms, Lung,Neoplasms, Pulmonary,Cancer, Lung,Cancer, Pulmonary,Cancers, Lung,Cancers, Pulmonary,Lung Cancers,Lung Neoplasm,Neoplasm, Lung,Neoplasm, Pulmonary,Pulmonary Cancers,Pulmonary Neoplasm
D002289 Carcinoma, Non-Small-Cell Lung A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy. Carcinoma, Non-Small Cell Lung,Non-Small Cell Lung Cancer,Non-Small Cell Lung Carcinoma,Non-Small-Cell Lung Carcinoma,Nonsmall Cell Lung Cancer,Carcinoma, Non Small Cell Lung,Carcinomas, Non-Small-Cell Lung,Lung Carcinoma, Non-Small-Cell,Lung Carcinomas, Non-Small-Cell,Non Small Cell Lung Carcinoma,Non-Small-Cell Lung Carcinomas
D002453 Cell Cycle The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE. Cell Division Cycle,Cell Cycles,Cell Division Cycles,Cycle, Cell,Cycle, Cell Division,Cycles, Cell,Cycles, Cell Division,Division Cycle, Cell,Division Cycles, Cell
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D004273 DNA, Neoplasm DNA present in neoplastic tissue. Neoplasm DNA
D006034 Glycyrrhetinic Acid An oleanolic acid from GLYCYRRHIZA that has some antiallergic, antibacterial, and antiviral properties. It is used topically for allergic or infectious skin inflammation and orally for its aldosterone effects in electrolyte regulation. Enoxolone,Glycyrrhetic Acid,Rhetinic Acid,Uralenic Acid,Arthrodont,Glyciram,Glycyram,Jintan,Po 12,12, Po,Acid, Glycyrrhetic,Acid, Glycyrrhetinic,Acid, Rhetinic,Acid, Uralenic
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000097002 Gap Junction beta-1 Protein A GAP JUNCTION beta subunit containing four transmembrane domains expressed in myelinating SCHWANN CELLS and is localized to peripheral MYELIN (e.g., noncompact myelin in the paranode and Schmitt-Lanterman incisures). Mutations in the human gene GJB1 are associated with X-linked CHARCOT-MARIE-TOOTH DISEASE type 1 (CMT1X). Connexin 32,Connexin 32 Protein,Cx32 Protein,GJB1 Protein,Gap Junction B1,Gap Junction beta1 Protein,Gap Junction beta 1 Protein,Protein, Connexin 32,Protein, Cx32,Protein, GJB1
D000230 Adenocarcinoma A malignant epithelial tumor with a glandular organization. Adenocarcinoma, Basal Cell,Adenocarcinoma, Granular Cell,Adenocarcinoma, Oxyphilic,Adenocarcinoma, Tubular,Adenoma, Malignant,Carcinoma, Cribriform,Carcinoma, Granular Cell,Carcinoma, Tubular,Adenocarcinomas,Adenocarcinomas, Basal Cell,Adenocarcinomas, Granular Cell,Adenocarcinomas, Oxyphilic,Adenocarcinomas, Tubular,Adenomas, Malignant,Basal Cell Adenocarcinoma,Basal Cell Adenocarcinomas,Carcinomas, Cribriform,Carcinomas, Granular Cell,Carcinomas, Tubular,Cribriform Carcinoma,Cribriform Carcinomas,Granular Cell Adenocarcinoma,Granular Cell Adenocarcinomas,Granular Cell Carcinoma,Granular Cell Carcinomas,Malignant Adenoma,Malignant Adenomas,Oxyphilic Adenocarcinoma,Oxyphilic Adenocarcinomas,Tubular Adenocarcinoma,Tubular Adenocarcinomas,Tubular Carcinoma,Tubular Carcinomas
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated

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