Abstract |
Although progress has been made in chemotherapeutic strategies against pancreatic cancer, overall survival has not significantly improved over the past decade. Thus, the development of better therapeutic regimens remains a high priority. Pancreatic cancer cell lines were treated with tamoxifen, a novel antitumor fusicoccin derivative (ISIR-042), and anticancer drugs, and their effects on cell growth, signaling and gene expression were determined. Xenografts of Panc-1 cells were treated with tamoxifen, ISIR-042 and 5-fluorouracil ( 5FU) to determine the effects on tumor growth. The inhibition of the growth of pancreatic cancer cells induced by tamoxifen was effectively reduced by α- tocopherol, a membrane stabilizer. ISIR-042 produced synergistic effects with tamoxifen in inhibiting cell growth. Tamoxifen elevated lipid peroxidation and the release of cytochrome c, and these effects of tamoxifen were reduced by α- tocopherol. ISIR-042 significantly inhibited colony formation and the expression of stemness-related genes of pancreatic cancer cells. The triple combination of tamoxifen, ISIR-042, and 5FU or gemcitabine was effective at inhibiting cell growth and the appearance of drug-resistant cells. This combined treatment significantly inhibited the growth of Panc-1 cells as xenografts without apparent adverse effects. The triple combination of tamoxifen and ISIR-042 with 5FU or gemcitabine may be highly effective against pancreatic cancer by overcoming resistance to therapy.
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Authors | Takaaki Miyake, Yoshio Honma, Takeshi Urano, Nobuo Kato, Junji Suzumiya |
Journal | International journal of oncology
(Int J Oncol)
Vol. 47
Issue 1
Pg. 315-24
(Jul 2015)
ISSN: 1791-2423 [Electronic] Greece |
PMID | 25936828
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Diterpenes
- Glycosides
- ISIR-042
- Tamoxifen
- Deoxycytidine
- fusicoccin
- Fluorouracil
- Gemcitabine
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Topics |
- Animals
- Antineoplastic Agents
(administration & dosage, pharmacology)
- Antineoplastic Combined Chemotherapy Protocols
(administration & dosage, pharmacology)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Deoxycytidine
(administration & dosage, analogs & derivatives, pharmacology)
- Diterpenes
(administration & dosage, pharmacology)
- Drug Resistance, Neoplasm
(drug effects)
- Drug Synergism
- Female
- Fluorouracil
(administration & dosage, pharmacology)
- Glycosides
(administration & dosage, pharmacology)
- Humans
- Lipid Peroxidation
(drug effects)
- Mice
- Mice, Nude
- Pancreatic Neoplasms
(drug therapy, metabolism)
- Tamoxifen
(administration & dosage, pharmacology)
- Xenograft Model Antitumor Assays
- Gemcitabine
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