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Targeting gene therapies enhance sensitivity to chemo‐ and radiotherapy of human oral squamous cell carcinoma
Author(s) -
Tanzawa Hideki,
Uzawa Katsuhiro,
Kasamatsu Atsushi,
EndoSakamoto Yosuke,
Saito Kengo,
Ogawara Katsunori,
Shiiba Masashi
Publication year - 2015
Publication title -
oral science international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.256
H-Index - 13
eISSN - 1881-4204
pISSN - 1348-8643
DOI - 10.1016/s1348-8643(15)00020-8
Subject(s) - radioresistance , cancer research , cisplatin , in vivo , pharmacology , medicine , radiation therapy , cancer , cancer cell , cilostazol , chemotherapy , biology , microbiology and biotechnology , aspirin
We have developed two methods to enhance the sensitivity of chemo‐ and/or radioresistant oral squamous carcinoma cells (OSCC). One is a method to inhibit a chemoresistant gene and to enhance sensitivity to chemotherapy. Most of the cases with resistance to cis‐diaminedichloro‐platinum II (cisplatin, CDDP) shows significant upregulated expression of phosphodiesterase 3B (PDE3B) and inhibition of PDE3B by cilostazol, which is clinically used as an antiplatelet drug for peripheral vascular disease, suppressing multidrug resistance‐associated proteins (MRPs), a subfamily of adenosine triphosphate (ATP)‐binding cassette (ABC) transporters, thus resulting in an increased amount of anticancer drugs such as CDDP. The combination usage of cilostazol and CDDP in vitro and in vivo indicated greater growth suppression of chemoresistant OSCC than that of either cilostazol alone or CDDP alone. The other method involves using a drug that inhibits radioresistance and enhances sensitivity to radiotherapy. Human oral squamous cancer cell lines exhibiting radioresistance show significant upregulated expression of the fibroblast growth factor receptor 3 (FGFR3). In vitro and in vivo, PD173074, a chemical agent inhibiting FGFR3, showed significant enhanced effect of radiation therapy on radioresistant cancer cells. These results provided novel information on which to base further mechanistic study on developing strategies to improve outcomes with concurrent chemo‐ and/or radiotherapy.