Document Detail


Low doses of cisplatin or gemcitabine plus Photofrin/photodynamic therapy: Disjointed cell cycle phase-related activity accounts for synergistic outcome in metastatic non-small cell lung cancer cells (H1299).
MedLine Citation:
PMID:  16546993     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We compared the effects of monotherapy (photodynamic therapy or chemotherapy) versus combination therapy (photodynamic therapy plus a specific drug) on the non-small cell lung cancer cell line H1299. Our aim was to evaluate whether the additive/synergistic effects of combination treatment were such that the cytostatic dose could be reduced without affecting treatment efficacy. Photodynamic therapy was done by irradiating Photofrin-preloaded H1299 p53/p16-null cells with a halogen lamp equipped with a bandpass filter. The cytotoxic drugs used were cis-diammine-dichloroplatinum [II] (CDDP or cisplatin) and 2',2'-difluoro-2'-deoxycytidine (gemcitabine). Various treatment combinations yielded therapeutic effects (trypan blue dye exclusion test) ranging from additive to clearly synergistic, the most effective being a combination of photodynamic therapy and CDDP. To gain insight into the cellular response mechanisms underlying favorable outcomes, we analyzed the H1299 cell cycle profiles and the expression patterns of several key proteins after monotherapy. In our conditions, we found that photodynamic therapy with Photofrin targeted G0-G1 cells, thereby causing cells to accumulate in S phase. In contrast, low-dose CDDP killed cells in S phase, thereby causing an accumulation of G0-G1 cells (and increased p21 expression). Like photodynamic therapy, low-dose gemcitabine targeted G0-G1 cells, which caused a massive accumulation of cells in S phase (and increased cyclin A expression). Although we observed therapeutic reinforcement with both drugs and photodynamic therapy, reinforcement was more pronounced when the drug (CDDP) and photodynamic therapy exert disjointed phase-related cytotoxic activity. Thus, if photodynamic therapy is appropriately tuned, the dose of the cytostatic drug can be reduced without compromising the therapeutic response.
Authors:
Elvira Crescenzi; Angela Chiaviello; Gianfranco Canti; Elena Reddi; Bianca Maria Veneziani; Giuseppe Palumbo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular cancer therapeutics     Volume:  5     ISSN:  1535-7163     ISO Abbreviation:  Mol. Cancer Ther.     Publication Date:  2006 Mar 
Date Detail:
Created Date:  2006-03-20     Completed Date:  2006-05-26     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  101132535     Medline TA:  Mol Cancer Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  776-85     Citation Subset:  IM    
Affiliation:
Dipartimento di Biologia e Patologia Cellulare e Molecolare L. Califano, Università di Napoli Federico II, Via S. Pansini 5, 80131 Naples, Italy.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / therapeutic use*
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Carcinoma, Non-Small-Cell Lung / drug therapy*,  secondary
Cisplatin / therapeutic use
Deoxycytidine / analogs & derivatives,  therapeutic use
Dihematoporphyrin Ether / therapeutic use
Dose-Response Relationship, Drug
G0 Phase / drug effects
G1 Phase / drug effects
Humans
Lung Neoplasms / drug therapy*,  pathology
Photochemotherapy*
Photosensitizing Agents / therapeutic use*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Photosensitizing Agents; 15663-27-1/Cisplatin; 951-77-9/Deoxycytidine; 97067-70-4/Dihematoporphyrin Ether; B76N6SBZ8R/gemcitabine

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