The effects of chemotherapeutic agents on differentiated chordoma cells

Laboratory investigation

Omer Faruk Bayrak Ph.D.1,2,3, Esra Aydemir M.Sc.1,4, Sukru Gulluoglu B.S.1, Fikrettin Sahin Ph.D.1, Serhat Sevli M.Sc.4, Mehmet Emir Yalvac M.Sc.1, Hasan Acar Ph.D.3, and Mustafa Ozen M.D., Ph.D.4
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  • 1 Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University, Istanbul;
  • | 2 Department of Medical Genetics, Yeditepe University Medical School and Yeditepe University Hospital, Istanbul;
  • | 3 Department of Medical Genetics, Selcuklu Medical School, Konya; and
  • | 4 Department of Medical Genetics, Cerrahpasa Medical School of Istanbul University, Istanbul, Turkey
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Object

Chordoma is a rare type of malignant bone tumor and is known to arise from the remnants of the notochord. Resistance to chemotherapy makes the treatment of chordoma difficult; therefore, new approaches need to be developed to cure this disease. Differentiation therapy, using various differentiating agents, is attracting oncologists as a common therapeutic method to treat other tumors. Based on forcing cells to mature into other lineages, differentiation therapy might be an available method to treat chordomas in addition to conventional therapies.

Methods

In this study a chordoma cell line, U-CH1, was exposed to several chemotherapeutic agents including vincristine, doxorubicin, cisplatin, etoposide, fludarabine, methotrexate, nilotinib, and imatinib mesylate under appropriate conditions. The first group of U-CH1 cells was exposed to drugs only and the second group of cells was exposed to the simultaneous treatment of 1 μM all-trans retinoic acid (ATRA) and chemotherapeutic agents in differentiation therapy. The efficacy of the differentiation method was assessed by measuring the viability of U-CH1 cells.

Results

Vincristine, doxorubicin, etoposide, cisplatin, and fludarabine, each at a concentration of 10 μM, decreased the number of chordoma cells when given alone down to 11%, 0%, 30%, 67%, and 3%, respectively. Etoposide and cisplatin, each at a concentration of 10 μM, reduced the percentage of viable chordoma cells in a more effective way when given with 1 μM ATRA simultaneously, reducing the number of viable cells to 14% and 9%, respectively. On the other hand, imatinib and nilotinib, each at a concentration of 3 μM, as well as 10 μM methotrexate, showed no decrease in the number of cancer cells.

Conclusions

The results suggest that chordoma cells may be treated using the differentiation method in a more effective way than when they are treated with chemotherapeutic agents alone. This new approach may be an alternative method to conventional therapies in the treatment of chordoma.

Abbreviations used in this paper:

ATRA = all-trans retinoic acid; DMSO = dimethyl sulfoxide; MTS = 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium; STAT3 = signal transducer and activator of transcription 3.

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