Targeting gene therapies enhance sensitivity to chemo‐ and radiotherapy of human oral squamous cell carcinoma

Abstract

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.

Nitrate increases cisplatin chemosensitivity of oral squamous cell carcinoma via REDD1/AKT signaling pathway

“…Combinations of platinum with several types of chemotherapeutics have been used to treat OSCC patients. However, the use of drug combinations increases the frequency of unpredictable severe side effects, including liver and kidney toxicity, gastrointestinal and hematologic toxicity and impaired immune-cell function (Tanzawa et al, 2015); these side effects markedly compromise the efficacy of platinumbased chemotherapy and result in chemotherapy failure (Gong et al, 2017). Therefore, development of strategies to effectively improve chemotherapy sensitivity while reducing its side effects is an ongoing challenge for OSCC chemotherapy.…”

FBLIM1 enhances oral cancer malignancy via modulation of the epidermal growth factor receptor pathway

“…OSCC‐derived cell lines (HSC‐2, HSC‐3, HSC‐4, KOSC‐2, Sa3, Ca9‐22, SAS, HO‐1‐u‐1, and HO‐1‐N‐1) were obtained from the Japanese Collection of Research Bioresources Cell Bank (Ibaraki, Osaka, Japan) or the RIKEN BioResource Center (Tsukuba, Ibaraki, Japan) . All OSCC cell lines were cultured in Dulbecco's modified Eagle medium (DMEM) (Sigma‐Aldrich, St. Louis, MO).…”

“…In the current study, we sought to clarify the clinical relevance of or the RIKEN BioResource Center (Tsukuba, Ibaraki, Japan). 18,19 All OSCC cell lines were cultured in Dulbecco's modified Eagle medium (DMEM) (Sigma-Aldrich, St. Louis, MO). We collected human normal oral keratinocytes (HNOKs), as normal controls in this research.…”

SYT12 plays a critical role in oral cancer and may be a novel therapeutic target

“…Eleven human OSCC-derived cell lines (HSC-2, HSC-3, HSC-3-M3, HSC-4, Sa3, Ca9-22, KOSC-2, SAS, SAS-H1, Ho-1-u-1, and Ho-1-N-1) were purchased from RIKEN BioResource Center (Tsukuba, Ibaraki, Japan) and the Japanese Collection of Research Bioresources Cell Bank (Ibaraki, Osaka, Japan) [11][12][13]. We obtained human normal oral keratinocyte (HNOKs) from young healthy patients and cultured the cells as described previously [14][15][16][17]. The cells used in this study were within 10 passages from thawing.…”