RT Journal Article SR Electronic T1 Murine Double Minute 2 Antagonist Nutlin-3 Enhanced Chemosensitivity in Esophageal Squamous Cell Carcinoma JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 2875 OP 2882 DO 10.21873/anticanres.15769 VO 42 IS 6 A1 KEN ITO A1 HIROTAKA ISHIDA A1 FUMIYOSHI FUJISHIMA A1 YASUHIRO NAKAMURA A1 TAKURO KONNO A1 KAZUE ISE A1 SHUKO HATA A1 YOHEI OZAWA A1 YUSUKE TANIYAMA A1 TAKASHI KAMEI A1 HIRONOBU SASANO YR 2022 UL http://ar.iiarjournals.org/content/42/6/2875.abstract AB 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 over-expressing MDM2.