Isoliquiritigenin inhibits tumor growth and protects the kidney and liver against chemotherapy-induced toxicity in a mouse xenograft model of colon carcinoma
Isoliquiritigenin inhibits tumor growth and protects the kidney and liver against chemotherapy-induced toxicity in a mouse xenograft model of colon carcinoma
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DOI：
10.1254/jphs.fp0071498
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发表时间：
2008-03-01
影响因子：
3.5
通讯作者：
Chung, Won Yoon
中科院分区：
文献类型：
--
作者：
Lee, Chang Ki;Son, Seung Hwa;Chung, Won Yoon
越来越多的注意力集中在研究化学预防剂与化疗药物联合使用时抑制癌细胞生长和毒性的效果。本研究的目的是确定异甘草素 (ISL) 是否有潜力作为顺铂化疗期间的有益补充剂。我们发现，单独施用ISL可显着减小CT-26细胞接种的BALB/c小鼠中实体瘤的大小，没有任何可检测到的肾毒性、肝毒性和氧化应激诱导，并且ISL以剂量依赖性方式降低CT-26小鼠结肠癌细胞的活力和DNA合成。 ISL不影响顺铂的治疗效果。此外，ISL 可抑制顺铂诱导的以血清肌酐和血尿素氮增加为特征的肾损伤，以及顺铂诱导的以血清丙氨酸转氨酶和天冬氨酸转氨酶增加为特征的肝损伤。在顺铂治疗前重复口服 ISL 可对顺铂介导的血清一氧化氮和组织脂质过氧化水平升高起到预防作用，并恢复组织中耗尽的 GSH 水平。因此，补充ISL可能是对抗癌症患者顺铂治疗副作用的有效方法。
A growing amount of attention has been focused on the investigation of the effects of chemopreventive agents on the inhibition of cancer cell growth and toxicity in combination with chemotherapeutics. The objective of this study was to determine whether isoliquiritigenin (ISL) has the potential to serve as a beneficial supplement during cisplatin chemotherapy. We found that the administration of ISL alone significantly reduced the size of the solid tumors in CT-26 cell-inoculated BALB/c mice, without any detectable induction of nephrotoxicity, hepatotoxicity, and oxidative stress, and ISL reduced the viability and DNA synthesis of CT-26 murine colon cancer cells in a dose-dependent manner. ISL did not affect the therapeutic efficacy of cisplatin. Furthermore, ISL suppressed cisplatin-induced kidney damage characterized by increases in serum creatinine and blood urea nitrogen, as well as cisplatin-induced liver damage characterized by increases in serum alanine aminotransferase and aspartate aminotransferase. The repeated oral administration of ISL prior to cisplatin treatment exerted a preventive effect on cisplatin-mediated increases in serum nitric oxide and tissue lipid peroxidation levels, and it recovered depleted GSH levels in the tissues. Therefore, supplementation with ISL may be an effective approach to counteracting the side effects of cisplatin therapy in cancer patients.