Abstract |
Orthotopic implantation of a metastatic cell line of Lewis lung carcinoma (LLC-MLN), which was isolated by an in vivo selection method, resulted in greater metastatic growth in mediastinal lymph nodes as compared with that of the original LLC cells. LLC-MLN cells also had increased invasive ability and activator protein-1 (AP-1) transcriptional activity as compared with the original LLC cells. This is well consistent with the previously reported finding that overexpression of AP-1 is associated with lymphatic metastasis in lung cancer patients. Oral administration of curcumin, which downregulates AP-1 transcription, significantly inhibited the mediastinal lymph node metastasis of orthotopically implanted LLC cells in a dose-dependent manner, but did not affect the tumor growth at the implantation site. Combined treatment with curcumin and an anti- cancer drug, cis- diamine-dichloroplatinum (CDDP), resulted in a marked inhibition of tumor growth at the implanted site and of lymphatic metastasis, and a significant prolongation of the survival time. The downregulation of transcriptional AP-1 activity by curcumin as seen in the dual luciferase assay caused inhibition of LLC cell invasion through the repression of expression of the mRNAs for urokinase-type plasminogen activator ( u-PA) and its receptor (u-PAR). Inhibition of AP-1 transcriptional activity may offer improved therapeutic efficacy for lung cancer patients with lymphatic metastasis.
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Authors | K Ichiki, N Mitani, Y Doki, H Hara, T Misaki, I Saiki |
Journal | Clinical & experimental metastasis
(Clin Exp Metastasis)
Vol. 18
Issue 7
Pg. 539-45
( 2000)
ISSN: 0262-0898 [Print] Netherlands |
PMID | 11688958
(Publication Type: Journal Article)
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Chemical References |
- Antineoplastic Agents
- Plaur protein, mouse
- RNA, Neoplasm
- Receptors, Cell Surface
- Receptors, Urokinase Plasminogen Activator
- Transcription Factor AP-1
- Urokinase-Type Plasminogen Activator
- Curcumin
- Cisplatin
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Topics |
- Animals
- Antineoplastic Agents
(pharmacology)
- Carcinoma, Lewis Lung
(genetics, metabolism, secondary)
- Cell Division
(drug effects)
- Cisplatin
(pharmacology)
- Curcumin
(pharmacology)
- Dose-Response Relationship, Drug
- Female
- Kinetics
- Lung Neoplasms
(genetics, metabolism, pathology)
- Lymphatic Metastasis
- Mediastinal Neoplasms
(pathology, secondary)
- Mice
- Mice, Inbred C57BL
- Neoplasm Invasiveness
- RNA, Neoplasm
(biosynthesis)
- Receptors, Cell Surface
(biosynthesis, genetics)
- Receptors, Urokinase Plasminogen Activator
- Transcription Factor AP-1
(metabolism)
- Urokinase-Type Plasminogen Activator
(biosynthesis, genetics)
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