Schisandrin B prevents doxorubicin-induced chronic cardiotoxicity and enhances its anticancer activity in vivo.
Schisandrin B prevents doxorubicin-induced chronic cardiotoxicity and enhances its anticancer activity in vivo.
复制标题
五味子乙素可预防阿霉素引起的慢性心脏毒性并增强其体内抗癌活性
DOI：
10.1371/journal.pone.0028335
复制
发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Hu X
中科院分区：
文献类型：
--
作者：
Xu Y;Liu Z;Sun J;Pan Q;Sun F;Yan Z;Hu X
研究背景如何在不影响蒽环类抗生素抗癌活性的前提下减轻其心脏毒性仍是一个亟待解决的问题。我们以前证明，五味子乙素B（Sch B）可以保护免受阿霉素（Dox）诱导的急性心脏毒性，通过增强心肌细胞谷胱甘肽氧化还原循环，可以减弱由Dox产生的氧化应激。在这项研究中，我们试图证明，如果Sch B也可以防止Dox诱导的慢性心脏毒性，一个更临床相关的问题，而不损害其抗癌活性。方法大鼠在腹膜内注射Dox（2.5 mg/kg）之前2小时经胃内给予载体或Sch B（50 mg/kg），每周一次，持续5周，累积剂量为Dox 12.5 mg/kg。末次给药后第6周和第12周，测定大鼠心功能，并对左心室进行组织学和超微结构检查。通过体外和体内对乳腺癌细胞系4 T1和肉瘤细胞系S180的生长抑制来评价Sch B增强的Dox抗癌活性。主要结果：Sch B预处理可明显减轻Dox引起的心功能丧失和心肌细胞结构损伤。Sch B能显著增强Dox对S180的细胞毒作用，增强Dox对4 T1的细胞毒作用。虽然我们没有观察到对植入的4 T1原发性肿瘤的这种增强，但在联合治疗组中，自发转移到肺的情况比Dox单独治疗组显著减少。结论Sch B对Dox所致的慢性心脏毒性具有保护作用，并能增强其抗肿瘤活性。据我们所知，Sch B是唯一被证明具有心脏保护剂和化疗增敏剂功能的分子，这可能适用于癌症治疗。
Background To mitigate the cardiotoxicity of anthracycline antibiotics without compromising their anticancer activities is still an issue to be solved. We previously demonstrated that schisandrin B (Sch B) could protect against doxorubicin (Dox)-induced acute cardiotoxicity via enhancing cardiomyocytic glutathione redox cycling that could attenuate oxidative stress generated from Dox. In this study, we attempted to prove if Sch B could also protect against Dox-induced chronic cardiotoxicity, a more clinically relevant issue, without compromising its anticancer activity. Methodology Rat was given intragastrically either vehicle or Sch B (50 mg/kg) two hours prior to i.p. Dox (2.5 mg/kg) weekly over a 5-week period with a cumulative dose of Dox 12.5 mg/kg. At the 6th and 12th week after last dosing, rats were subjected to cardiac function measurement, and left ventricles were processed for histological and ultrastructural examination. Dox anticancer activity enhanced by Sch B was evaluated by growth inhibition of 4T1, a breast cancer cell line, and S180, a sarcoma cell line, in vitro and in vivo. Principal Findings Pretreatment with Sch B significantly attenuated Dox-induced loss of cardiac function and damage of cardiomyocytic structure. Sch B substantially enhanced Dox cytotoxicities toward S180 in vitro and in vivo in mice, and increased Dox cytotoxcity against 4T1 in vitro. Although we did not observe this enhancement against the implanted 4T1 primary tumor, the spontaneous metastasis to lung was significantly reduced in combined treatment group than Dox alone group. Conclusion Sch B is capable of protecting Dox-induced chronic cardiotoxicity and enhancing its anticancer activity. To the best of our knowledge, Sch B is the only molecule ever proved to function as a cardioprotective agent as well as a chemotherapeutic sensitizer, which is potentially applicable for cancer treatment.
登录
查看更多内容
影响因子：
3
作者：
Pan, QR;Lu, QH;Hu, X
通讯作者：
Hu, X
影响因子：
3
作者：
Huang, Min;Jin, Jing;Liu, Geng Tao
通讯作者：
Liu, Geng Tao
Schisandrin B对DNA损伤反应中ATR蛋白激酶活性的抑制。
影响因子：
14.9
作者：
Nishida H;Tatewaki N;Nakajima Y;Magara T;Ko KM;Hamamori Y;Konishi T
通讯作者：
Konishi T
影响因子：
11.5
作者：
Li, Ling;Pan, Qiangrong;Hu, Xun
通讯作者：
Hu, Xun
影响因子：
2
作者：
Chen, Na;Ko, Kam Ming
通讯作者：
Ko, Kam Ming