Osman Abdel-Moneim M, Telity Suad A, Telity Saud A, Damanhouri Zoheir A, Al-Harthy Sameer E, Al-Kreathy Huda M, Ramadan Wafaa S, Elshal Mohamed F, Khan Lateef M, Kamel Fatemah
Pharmacology Department, Faculty of Medicine, King Abdulaziz University, P.O. box 80205, Jeddah, Saudi Arabia ; Pharmacology unit, National Cancer Institute, Cairo University, Cairo, 11796 Egypt.
Pharmacology Department, Faculty of Medicine, King Abdulaziz University, P.O. box 80205, Jeddah, Saudi Arabia.
Cancer Cell Int. 2015 Feb 4;15:6. doi: 10.1186/s12935-014-0152-2. eCollection 2015.
Cisplatin (CIS) is one of the most effective anticancer drug used in the treatment of several solid tumors .Its use is limited by its nephrotoxicity. The present study was designed to assess the role of a natural product resveratrol (RSVL) on sensitization of mammary carcinoma (Ehrlich ascites carcinoma) to the action of CIS and the possible protective effect against CIS-induced nephrotoxicity in rats.
The percent survival of female tumor bearing mice was used for determination the cytotoxic activity of CIS in the presence or the absence of RSVL. Uptake and cell cycle effect, serum creatinine (CREA), blood urea nitrogen (BUN), Reduced Glutathione (GSH) and histopatholgical examination of kidney tissues after CIS and/or RSVL therapy were also investigated.
RSVL increased the intracellular level of CIS in EAC cells and there was a strong correlation between the high cellular level of CIS and its cytotoxicity. CIS at a dose level of 5 mg/kg increased the mean survival time of female tumor bearing mice to 25 days compared with 17 days for tumor-bearing control mice. Administration of RSVL at a dose level of 25 mg/kg simultaneously with CIS increased the mean survival time to 48 days with 60% survival of the tumor-bearing animals. Cell cycle analysis of tumor cells showed that CIS treatment decreases the proliferation index of tumor cells while in presence of RSVL there was more significant inhibitions. Also, CIS treatment caused increase in level of creatinine and blood urea with significant decrease in the GSH level. While, in the presence of RSVL, level of creatinine and blood urea restored to control level.
This study suggests that RSVL could increase the cytotoxic activity of CIS and protect against its nephrotoxicity.
顺铂（CIS）是治疗多种实体瘤最有效的抗癌药物之一。其应用因肾毒性而受到限制。本研究旨在评估天然产物白藜芦醇（RSVL）对乳腺癌（艾氏腹水癌）对CIS作用的致敏作用以及对大鼠CIS诱导的肾毒性的可能保护作用。
使用雌性荷瘤小鼠的存活率来测定在有或没有RSVL的情况下CIS的细胞毒性活性。还研究了CIS和/或RSVL治疗后肾脏组织的摄取和细胞周期效应、血清肌酐（CREA）、血尿素氮（BUN）、还原型谷胱甘肽（GSH）以及组织病理学检查。
RSVL增加了艾氏腹水癌细胞中CIS的细胞内水平，并且CIS的高细胞水平与其细胞毒性之间存在很强的相关性。剂量为5mg/kg的CIS将雌性荷瘤小鼠的平均存活时间提高到25天，而荷瘤对照小鼠为17天。与CIS同时给予剂量为25mg/kg的RSVL可将平均存活时间提高到48天，荷瘤动物的存活率为60%。肿瘤细胞的细胞周期分析表明，CIS治疗降低了肿瘤细胞的增殖指数，而在有RSVL的情况下抑制作用更显著。此外，CIS治疗导致肌酐和血尿素水平升高，GSH水平显著降低。而在有RSVL的情况下，肌酐和血尿素水平恢复到对照水平。
本研究表明，RSVL可以增加CIS的细胞毒性活性并防止其肾毒性。
