Murine Double Minute 2 Antagonist Nutlin-3 Enhanced Chemosensitivity in Esophageal Squamous Cell Carcinoma

Ken Ito, Hirotaka Ishida, Fumiyoshi Fujishima, Yasuhiro Nakamura, Takuro Konno, Kazue Ise, Shuko Hata, Yohei Ozawa, Yusuke Taniyama, Takashi Kamei, Hironobu Sasano

研究成果: Article査読


Background/Aim: Murine double minute 2 (MDM2) is well known to inhibit p53 function and its over-expression is associated with poor prognosis in several human malignancies. Nutlin-3, a small-molecule inhibitor of MDM2, exerts antitumor effects on various solid tumors harboring wild-type p53. We aimed to clarify its effects on esophageal cancer. Materials and Methods: We first examined the potential antitumor effects of nutlin-3 according to MDM2 status using esophageal carcinoma cell lines (KYSE 170/180). We then immunolocalized MDM2 immunoreactivity in 62 surgical cases of esophageal squamous cell carcinoma undergoing neoadjuvant chemotherapy followed by esophagectomy and correlated the findings with clinicopathological variables. Results: MDM2 mRNA expression in KYSE 170 was significantly higher than that in KYSE 180 cells. No significant changes were detected in both cell lines when nutlin-3 was added. However, cell proliferation was significantly decreased in KYSE 170 cells treated with nutlin-3 and cisplatin compared to cisplatin alone but not in KYSE 180. MDM2 immunoreactivity was also significantly associated with poor sensitivity to neoadjuvant chemotherapy in the cases examined. Conclusion: The combination of nutlin-3 with chemotherapeutic agents may become a novel therapeutic strategy in esophageal cancer overexpressing MDM2.

ジャーナルAnticancer research
出版ステータスPublished - 2022 6月

ASJC Scopus subject areas

  • 腫瘍学
  • 癌研究


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