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硒与阿霉素或紫杉醇联合使用对几种不同癌细胞的影响。

Effect of selenium in combination with Adriamycin or Taxol on several different cancer cells.

作者信息

Vadgama J V, Wu Y, Shen D, Hsia S, Block J

机构信息

Department of Internal Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA 90059, USA.

出版信息

Anticancer Res. 2000 May-Jun;20(3A):1391-414.

Abstract

The anti-neoplastic properties of an Selenium compound were studied in vitro on several tumor cell lines: Breast (MCF-7, MCF-10, SKBR-3, BCAP37), Lung (RH2), Prostate (LNCap and PC-3), Colon (T84, Caco-2), Small Intestine (HCF8), and Liver (HepG2). We also examined additive or synergistic effect of Selenium in combination with standard anti-cancer drugs, Adriamycin (Doxorubicin) and Taxol. The effect of Selenium was assessed by apoptosis; DNA synthesis; growth rate by MTT assay; uptake of amino acid MeAIB by System A; and morphological changes. Our results demonstrate that MCF-7 and SKBR-3 showed increase in apoptosis as measured by DNA fragmentation and increase in "rounded" cells and membrane "blebbing", decrease in MeAIB uptake, and decrease in DNA synthesis. These changes were Selenium dose dependent with optimal inhibition at Selenium concentration between 4 and 40 ng/ml after 72 hrs of treatment. Similar observations were made with RH2, HCF8, Caco-2, and HepG2 cells. In contrast, LNCap, PC-3, and T-84 were not significantly affected by Selenium. However, addition of Adriamycin or Taxol in combination with Selenium caused small but significant inhibition of prostate cancer cells LNCap and PC-3. Addition of chemotherapeutic agents either Taxol or Doxorubicin with Selenium caused further inhibition of MCF-7, SKBR-3, RH2, HCF8, and HepG2 cells. In conclusion, Selenium has a significant anti-neoplastic effect on breast, lung, liver, and small intestinal tumor cells. Supplementation of Selenium enhanced chemotherapeutic effect of Taxol and Doxorubicin in these cells beyond that seen with the chemotherapeutic drugs used alone. These in vitro studies on several cancer cell lines suggest a potential benefit of Selenium-enhancement of anticancer effects other systems, and therefore offer further relevance to clinical trials efforts.

摘要

在体外研究了一种硒化合物对几种肿瘤细胞系的抗肿瘤特性,这些细胞系包括:乳腺癌(MCF-7、MCF-10、SKBR-3、BCAP37)、肺癌(RH2)、前列腺癌(LNCap和PC-3)、结肠癌(T84、Caco-2)、小肠癌(HCF8)和肝癌(HepG2)。我们还研究了硒与标准抗癌药物阿霉素(多柔比星)和紫杉醇联合使用时的相加或协同作用。通过细胞凋亡、DNA合成、MTT法检测生长速率、系统A对氨基酸MeAIB的摄取以及形态变化来评估硒的作用。我们的结果表明,通过DNA片段化检测,MCF-7和SKBR-3细胞的凋亡增加,“圆形”细胞和细胞膜“起泡”增加,MeAIB摄取减少,DNA合成减少。这些变化呈硒剂量依赖性,在处理72小时后,硒浓度在4至40 ng/ml之间时抑制作用最佳。在RH2、HCF8、Caco-2和HepG2细胞中也观察到了类似的现象。相比之下,LNCap、PC-3和T-84细胞对硒没有显著反应。然而,阿霉素或紫杉醇与硒联合使用对前列腺癌细胞LNCap和PC-3有轻微但显著的抑制作用。化疗药物紫杉醇或多柔比星与硒联合使用对MCF-7、SKBR-3、RH2、HCF8和HepG2细胞有进一步的抑制作用。总之,硒对乳腺癌、肺癌、肝癌和小肠肿瘤细胞具有显著的抗肿瘤作用。补充硒增强了紫杉醇和多柔比星在这些细胞中的化疗效果,超过了单独使用化疗药物的效果。这些对几种癌细胞系的体外研究表明,硒增强抗癌作用对其他系统可能有益,因此与临床试验的努力具有进一步的相关性。

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