Preclinical rationale for synergistic interaction of pemetrexed and cytotoxic nucleoside analogues

Oguri,Tetsuya; Ozasa,Hiroaki; Uemura,Takehiro; Takakuwa,Osamu; Kunii,Eiji; Kasai,Daishi; Ohkubo,Hirotsugu; Miyazaki,Mikinori; Maeno,Ken; Sato,Shigeki

doi:10.3892/ol.2012.773

September 2012 Volume 4 Issue 3

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September 2012 Volume 4 Issue 3

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Article

Preclinical rationale for synergistic interaction of pemetrexed and cytotoxic nucleoside analogues

Authors:
- Tetsuya Oguri
- Hiroaki Ozasa
- Takehiro Uemura
- Osamu Takakuwa
- Eiji Kunii
- Daishi Kasai
- Hirotsugu Ohkubo
- Mikinori Miyazaki
- Ken Maeno
- Shigeki Sato
View Affiliations / Copyright

Affiliations: Department of Medical Oncology and Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan
Pages: 571-575
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Published online on: June 26, 2012

https://doi.org/10.3892/ol.2012.773
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Abstract

Cytotoxic nucleoside analogues are widely used in cancer chemotherapy. We used the cytosine arabinoside (Ara-C)-resistant erythroleukaemia cell line K562 and the Ara-C-sensitive myeloid leukaemia cell line HL60 to examine the differential expression of molecular markers. We found increased expression levels of deoxycytidine kinase (dCK) and human equilibrative nucleoside transporter 1 (hENT1) and decreased levels of multidrug resistance protein 5 (ABCC5) and ribonucleoside reductase subunit M1 (RRM1) expression in Ara-C-sensitive HL60 cells. We previously established the pemetrexed (MTA)-resistant small cell lung cancer cell lines PC6/MTA-0.4 and PC6/MTA-1.6 and found that MTA-resistant cells are more sensitive to gemcitabine (GEM) and Ara-C compared with parental PC-6 cells. We examined the molecular markers for GEM and Ara-C sensitivity in MTA-resistant cells and found increased gene expression of dCK and hENT1. Furthermore, treatment with MTA resulted in increased expression of dCK and hENT1 and decreased expression of ABCC5 and RRM1, concomitant with the alteration of the resistance to Ara-C in Ara-C-resistant K562 cells. These results provide evidence that the chemotherapeutic activity of the combination of MTA and cytotoxic nucleoside analogues is synergistic with regard to the alteration of metabolic molecules.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Preclinical rationale for synergistic interaction of pemetrexed and cytotoxic nucleoside analogues

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