Experimental study of combination therapy with S-1 against pancreatic cancer
| Autor: | Yoshinori Yamada, Yoshihito Morimoto, Osamu Takeuchi, Ken Sasaki, Asako Takizawa, Yukio Suzuki, Koichiro Atsuda, Fumiki Asanuma, Osamu Hiraku, Jun Yoshizawa, Gaku Inoue |
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| Rok vydání: | 2008 |
| Předmět: |
Oncology
Cancer Research Pancreatic disease Pyridines Apoptosis Toxicology Deoxycytidine Mice Pharmacology (medical) media_common Mice Inbred BALB C Cell Cycle Combination chemotherapy Drug Synergism Drug Combinations Drug Therapy Combination Female Fluorouracil medicine.drug Drug medicine.medical_specialty Combination therapy Paclitaxel medicine.drug_class media_common.quotation_subject Mitomycin Antineoplastic Agents Irinotecan Antimetabolite Inhibitory Concentration 50 Pancreatic cancer Internal medicine Cell Line Tumor medicine Animals Humans Cell Proliferation Tegafur Pharmacology business.industry Cancer medicine.disease Xenograft Model Antitumor Assays Gemcitabine Pancreatic Neoplasms Oxonic Acid Doxorubicin Immunology Camptothecin Cisplatin business |
| Zdroj: | Cancer chemotherapy and pharmacology. 64(6) |
| ISSN: | 1432-0843 |
| Popis: | To determine the most effective combination chemotherapy with S-1 against pancreatic cancer and to clarify the mechanism of synergy between S-1 and the partner drug.We tested a combination of S-1 with the following antitumor drugs in an in vitro MTT assay against pancreatic cancer cell line MIA PaCa-2: gemcitabine (GEM), cisplatin (CDDP), irinotecan (CPT-11), mitomycin C, adriamycin, and paclitaxel. The efficacy of S-1, GEM, and a combination of S-1 and GEM was also tested in vivo by administering S-1 (10 mg/kg) orally to nude mice five times a week for 3 weeks, and GEM (100 mg/kg) intravenously every 2-3 days for a total of six times. A treated-to-control ratio (T/C) of relative mean tumor weight values less than 50% was determined to be effective. Furthermore, we investigated the mechanism of the synergistic effect of S-1 and GEM on the cell cycle by flow cytometry, because both S-1 and GEM are known as antimetabolic drugs. To verify cell death induced by a change in the distribution of the cell cycle phases, we investigated apoptosis by sub-G1 analysis and a TUNEL assay.From classical isobolography analysis of the in vitro MTT assay, the combination of S-1 plus GEM was found to be the most effective of the combinations tested. In vivo, T/C (percentage) with the combination of S-1 plus GEM was 48.2%, which was lower than that of S-1 or GEM alone, and the combination enhanced antitumor activity. Cell cycle analysis showed greater cell cycle delay with the combination treatment (S-1 plus GEM) than for each single drug treatment, and apoptotic cells were detected only in treatments including GEM.The combination chemotherapy of S-1 and GEM appears to be useful for pancreatic cancer. Both cycle delay by S-1 plus GEM and apoptosis induced by GEM are involved in this synergistic mechanism. |
| Databáze: | OpenAIRE |
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