Olanzapine, an Atypical Antipsychotic, Inhibits Survivin Expression and Sensitizes Cancer Cells to Chemotherapeutic Agents

奥氮平是一种非典型抗精神病药,可抑制 Survivin 表达并使癌细胞对化疗药物敏感

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作者:Tomomi Sanomachi, Shuhei Suzuki, Kenta Kuramoto, Hiroyuki Takeda, Hirotsugu Sakaki, Keita Togashi, Shizuka Seino, Takashi Yoshioka, Masashi Okada, Chifumi Kitanaka

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. Materials and

Conclusion

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.

Methods

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.

Results

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.

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