2. Academic Validation
  3. Synergetic Effects of PARP Inhibitor AZD2281 and Cisplatin in Oral Squamous Cell Carcinoma in Vitro and in Vivo

Synergetic Effects of PARP Inhibitor AZD2281 and Cisplatin in Oral Squamous Cell Carcinoma in Vitro and in Vivo

  • Int J Mol Sci. 2016 Feb 24;17(3):272. doi: 10.3390/ijms17030272.
Masaaki Yasukawa 1,  Hisako Fujihara 2 3,  Hiroaki Fujimori 4 5,  Koji Kawaguchi 6,  Hiroyuki Yamada 7,  Ryoko Nakayama 8,  Nanami Yamamoto 9,  Yuta Kishi 10,  Yoshiki Hamada 11,  Mitsuko Masutani 12 13
Affiliations

Affiliations

  • 1 Department of Oral and Maxillofacial Surgery, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama, Kanagawa 230-8501, Japan. yasukawa-masaaki@tsurumi-u.ac.jp.
  • 2 Department of Oral and Maxillofacial Surgery, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama, Kanagawa 230-8501, Japan. fujihara-h@tsurumi-u.ac.jp.
  • 3 Department of Oral Hygiene, Tsurumi Junior College, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama, Kanagawa 230-8501, Japan. fujihara-h@tsurumi-u.ac.jp.
  • 4 Division of Chemotherapy and Translational Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. hisakuma@ncc.go.jp.
  • 5 Department of Frontier Life Science, Graduate School of Biochemical Science, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan. hisakuma@ncc.go.jp.
  • 6 Department of Oral and Maxillofacial Surgery, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama, Kanagawa 230-8501, Japan. kawaguchi-k@tsurumi-u.ac.jp.
  • 7 Division of Maxillofacial Surgery, Department of Oral and Maxillofacial Surgery, School of Dentistry, Iwate Medical University 19-1 Uchimaru, Morioka Iwate 020-8050, Japan. yamadah@iwate-med.ac.jp.
  • 8 Department of Pathology, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama, Kanagawa 230-8501, Japan. nakayama-r@tsurumi-u.ac.jp.
  • 9 Department of Oral and Maxillofacial Surgery, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama, Kanagawa 230-8501, Japan. yamamoto-nanami@tsurumi-u.ac.jp.
  • 10 Department of Oral and Maxillofacial Surgery, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama, Kanagawa 230-8501, Japan. kishi-y@tsurumi-u.ac.jp.
  • 11 Department of Oral and Maxillofacial Surgery, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama, Kanagawa 230-8501, Japan. hamada-y@tsurumi-u.ac.jp.
  • 12 Division of Chemotherapy and Translational Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. mmasutan@ncc.go.jp.
  • 13 Department of Frontier Life Science, Graduate School of Biochemical Science, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan. mmasutan@ncc.go.jp.
PMID: 26927065 DOI: 10.3390/ijms17030272
Abstract

Cisplatin is a commonly used chemotherapeutic drug for treatment of oral carcinoma, and combinatorial effects are expected to exert greater therapeutic efficacy compared with monotherapy. Poly(ADP-ribosyl)ation is reported to be involved in a variety of cellular processes, such as DNA repair, cell death, telomere regulation, and genomic stability. Based on these properties, poly(ADP-ribose) polymerase (PARP) inhibitors are used for treatment of cancers, such as BRCA1/2 mutated breast and ovarian cancers, or certain solid cancers in combination with anti-cancer drugs. However, the effects on oral Cancer have not been fully evaluated. In this study, we examined the effects of PARP Inhibitor on the survival of human oral Cancer cells in vitro and xenografted tumors derived from human oral Cancer cells in vivo. In vitro effects were assessed by microculture tetrazolium and survival assays. The PARP Inhibitor AZD2281 (olaparib) showed synergetic effects with cisplatin in a dose-dependent manner. Combinatorial treatment with cisplatin and AZD2281 significantly inhibited xenografted tumor growth compared with single treatment of cisplatin or AZD2281. Histopathological analysis revealed that cisplatin and AZD2281 increased TUNEL-positive cells and decreased Ki67- and CD31-positive cells. These results suggest that PARP inhibitors have the potential to improve therapeutic strategies for oral Cancer.

Keywords

PARP inhibitor; cisplatin; oral cancer; xenografted tumor.

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