Department of Neurology, Oregon Health and Sciences University, Portland, OR 97239, USA.
Anticancer Res. 2013 Jun;33(6):2391-400.
Ovarian cancer is commonly treated with cisplatin/paclitaxel but many tumors become resistant. Acetaminophen reduced glutathione and enhanced chemotherapy efficacy in hepatic cancer treatment. The objective of this study was to examine if acetaminophen enhances the cytotoxicity of cisplatin/paclitaxel in ovarian cancer.
SKOV3 human ovarian carcinoma cells in vitro and a subcutaneous tumor nude rat model were used and treated with cisplatin/paclitaxel with or without acetaminophen.
In vitro, acetaminophen enhanced apoptosis induced by cisplatin and paclitaxel with similar effects on glutathione, reactive oxygen species and mitochondrial membrane potential, but different effects on nuclear factor erythroid 2-related factor 2 (NRF2) translocation. In vivo, acetaminophen was uniformly distributed in tissues and significantly reduced hepatic glutathione. Acetaminophen enhanced the cisplatin chemotherapeutic effect by reducing tumor recurrence.
Our results suggest that acetaminophen as a chemoenhancing adjuvant could improve the efficacy of cisplatin and paclitaxel in treating patients with ovarian carcinoma and other tumor types.
卵巢癌通常采用顺铂/紫杉醇治疗，但许多肿瘤会产生耐药性。对乙酰氨基酚还原型谷胱甘肽可增强肝癌的化疗疗效。本研究旨在研究对乙酰氨基酚是否可增强卵巢癌细胞中顺铂/紫杉醇的细胞毒性。
体外培养 SKOV3 人卵巢癌细胞，并建立皮下肿瘤裸鼠模型，用顺铂/紫杉醇联合或不联合对乙酰氨基酚进行治疗。
体外实验中，对乙酰氨基酚增强了顺铂和紫杉醇诱导的细胞凋亡，对谷胱甘肽、活性氧和线粒体膜电位有相似的影响，但对核因子红细胞 2 相关因子 2（NRF2）转位的影响不同。体内实验中，对乙酰氨基酚在组织中均匀分布，显著降低了肝脏中的谷胱甘肽水平。对乙酰氨基酚通过降低肿瘤复发率增强了顺铂的化疗效果。
我们的研究结果表明，对乙酰氨基酚作为化疗增强佐剂，可提高顺铂和紫杉醇治疗卵巢癌和其他肿瘤类型患者的疗效。
