Sanomachi Tomomi, Suzuki Shuhei, Kuramoto Kenta, Takeda Hiroyuki, Sakaki Hirotsugu, Togashi Keita, Seino Shizuka, Yoshioka Takashi, Okada Masashi, Kitanaka Chifumi
Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan.
Department of Clinical Oncology, Yamagata University School of Medicine, Yamagata, Japan.
Anticancer Res. 2017 Nov;37(11):6177-6188. doi: 10.21873/anticanres.12067.
BACKGROUND/AIM: Olanzapine, an atypical antipsychotic, is now increasingly used as an off-label indication for the management of cancer patients with chemotherapy-induced nausea and vomiting (CINV). However, how olanzapine affects cancer cells per se remains poorly understood.
The effects of olanzapine treatment and survivin knockdown, alone or in combination with chemotherapeutic agents, on survivin expression and cell viability were investigated in human cancer cell lines.
Olanzapine reduced survivin expression in lung and pancreatic cancer stem cell (CSC) lines and sensitized them to chemotherapeutic agents such as 5-fluorouracil, gemcitabine, and cisplatin in a survivin expression-dependent manner. Olanzapine also reduced survivin expression and chemosensitized serum-cultured, non-CSC ovarian cancer cells that expressed survivin.
Olanzapine may benefit cancer patients not only as an antiemetic for CINV, but also by enhancing the effects of chemotherapeutic agents through down-regulation of survivin, which has been implicated in multidrug chemoresistance.
背景/目的：奥氮平是一种非典型抗精神病药物，目前越来越多地被用于癌症患者化疗引起的恶心和呕吐（CINV）的非适应证治疗。然而，奥氮平本身如何影响癌细胞仍知之甚少。
在人癌细胞系中研究了奥氮平单独或与化疗药物联合处理以及敲低生存素对生存素表达和细胞活力的影响。
奥氮平降低了肺癌和胰腺癌干细胞（CSC）系中的生存素表达，并以生存素表达依赖的方式使它们对5-氟尿嘧啶、吉西他滨和顺铂等化疗药物敏感。奥氮平还降低了表达生存素的血清培养的非CSC卵巢癌细胞中的生存素表达并使其化疗增敏。
奥氮平可能不仅作为CINV的止吐药使癌症患者受益，还可通过下调生存素增强化疗药物的效果，生存素与多药化疗耐药有关。
