Combination therapy of 5-fluorouracil with rapamycin for hormone receptor-negative human breast cancer.

Abstract

AIM:

To determine a novel chemotherapeutic concept for hormone receptor-negative and HER2-positive breast cancer, a high progression form of the disease for which treatment has been difficult. A combination therapy of 5-fluorouracil (5-FU) with rapamycin (Rap) was examined.

MATERIALS AND METHODS:

The growth inhibitory effect of treatment was evaluated by an MTT assay and cellular signal/apoptotic pathways were investigated by Western blotting and Hoechst 33342 staining.

RESULTS:

Rap was shown to induce an inhibitory effect on the phosphorylation of mTOR and p70S6K. The expression of thymidine synthase (TS) was decreased by Rap. The addition of 5-FU to Rap was found to increase cell death. The Hoechst 33342 assay showed that apoptosis was increased by the combination of 5-FU and Rap in comparison to 5FU alone.

CONCLUSION:

5-FU is more effective in combination with the TS-reducing action of Rap, even for highly HER2-expressing breast cancer cells.

• Authors: Yoshiki Hosono, Shinji Osada, Masahito Nawa, Takao Takahashi, Kazuya Yamaguchi, Yoshihiro Kawaguchi, Kazuhiro Yoshida
• Journal: Anticancer research (Anticancer Res) Vol. 30 Issue 7 Pg. 2625-30 (Jul 2010) ISSN: 1791-7530 [Electronic] Greece
• PMID: 20682991 (Publication Type: Journal Article)

Chemical References

• Intracellular Signaling Peptides and Proteins
• Receptors, Estrogen
• Receptors, Progesterone
• MTOR protein, human
• Receptor, ErbB-2
• Protein Serine-Threonine Kinases
• Proto-Oncogene Proteins c-akt
• Ribosomal Protein S6 Kinases, 70-kDa
• TOR Serine-Threonine Kinases
• Extracellular Signal-Regulated MAP Kinases
• Fluorouracil
• Sirolimus

Topics

• Antineoplastic Combined Chemotherapy Protocols (pharmacology)
• Breast Neoplasms (drug therapy, metabolism)
• Cell Line, Tumor
• Drug Synergism
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Female
• Fluorouracil (administration & dosage)
• Humans
• Intracellular Signaling Peptides and Proteins (metabolism)
• Phosphorylation (drug effects)
• Protein Serine-Threonine Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Receptor, ErbB-2 (biosynthesis)
• Receptors, Estrogen (biosynthesis)
• Receptors, Progesterone (biosynthesis)
• Ribosomal Protein S6 Kinases, 70-kDa (metabolism)
• Signal Transduction (drug effects)
• Sirolimus (administration & dosage)
• TOR Serine-Threonine Kinases