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新型席夫碱二氯(4-甲氧基-2-{[2-(哌嗪-4-鎓-1-基)乙基]亚氨基甲基}苯酚根)镉配合物对大鼠偶氮甲烷诱导的结直肠癌中结肠异常隐窝灶的化学预防作用

Chemoprevention of Colonic Aberrant Crypt Foci by Novel Schiff Based Dichlorido(4-Methoxy-2-{[2-(Piperazin-4-Ium-1-Yl)Ethyl]Iminomethyl}Phenolate)Cd Complex in Azoxymethane-Induced Colorectal Cancer in Rats.

作者信息

Hajrezaie Maryam, Shams Keivan, Moghadamtousi Soheil Zorofchian, Karimian Hamed, Hassandarvish Pouya, Emtyazjoo Mozhgan, Zahedifard Maryam, Majid Nazia Abdul, Mohd Ali Hapipah, Abdulla Mahmood Ameen

机构信息

1] Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia [2] Institute of Biological Science, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.

Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.

出版信息

Sci Rep. 2015 Jul 23;5:12379. doi: 10.1038/srep12379.

Abstract

Schiff-based complexes as a source of cancer chemotherapeutic compounds have been subjected to the variety of anticancer studies. The in-vitro analysis confirmed the CdCl2(C14H21N3O2) complex possess cytotoxicity and apoptosis induction properties in colon cancer cells, so lead to investigate the inhibitory efficiency of the compound on colonic aberrant crypt foci (ACF). Five groups of adult male rats were used in this study: Vehicle, cancer control, positive control groups and the groups treated with 25 and 50 mg/kg of complex for 10 weeks. The rats in vehicle group were injected subcutaneously with 15 mg/kg of sterile normal saline once a week for 2 weeks and orally administered with 5% Tween-20 (5 ml/kg) for 10 weeks, other groups were injected subcutaneously with 15 mg/kg azoxymethane once a week for 2 weeks. The rats in positive groups were injected intra-peritoneally with 35 mg/kg 5-Flourouracil four times in a month. Administration of the complex suppressed total colonic ACF formation up to 73.4% (P < 0.05). The results also showed that treatment with the complex significantly reduced the level of malondialdehyde while increasing superoxide dismutase and catalase activities. Furthermore, the down-regulation of PCNA and Bcl2 and the up-regulation of Bax was confirmed by immunohistochemical staining.

摘要

基于席夫碱的配合物作为癌症化疗化合物的来源,已经进行了各种抗癌研究。体外分析证实,CdCl2(C14H21N3O2)配合物在结肠癌细胞中具有细胞毒性和诱导凋亡的特性,因此导致对该化合物对结肠异常隐窝灶(ACF)的抑制效率进行研究。本研究使用了五组成年雄性大鼠:溶剂对照组、癌症对照组、阳性对照组以及用25和50mg/kg配合物处理10周的组。溶剂对照组的大鼠每周皮下注射15mg/kg无菌生理盐水,共2周,并口服5%吐温-20(5ml/kg),共10周,其他组每周皮下注射15mg/kg氧化偶氮甲烷,共2周。阳性组的大鼠每月腹腔注射35mg/kg 5-氟尿嘧啶4次。配合物的给药可抑制总结肠ACF形成达73.4%(P<0.05)。结果还表明,配合物处理显著降低了丙二醛水平,同时提高了超氧化物歧化酶和过氧化氢酶活性。此外,免疫组织化学染色证实了PCNA和Bcl2的下调以及Bax的上调。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/282d/4511874/a1a9285e9be1/srep12379-f1.jpg

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