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丹参可提高结肠癌患者的生存率,二氢异丹参酮 I 通过凋亡和 skp2 信号通路抑制结肠癌细胞的增殖。

Danshen improves survival of patients with colon cancer and dihydroisotanshinone I inhibit the proliferation of colon cancer cells via apoptosis and skp2 signaling pathway.

机构信息

Department of Chinese Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan.

Division of Colon and Rectal Surgery, Department of Surgery, Chang Gung Memorial Hospital Chiayi, Chiayi, Taiwan; Chang Gung University College of Medicine, Taoyuan, Taiwan.

出版信息

J Ethnopharmacol. 2017 Sep 14;209:305-316. doi: 10.1016/j.jep.2017.08.011. Epub 2017 Aug 12.

DOI:10.1016/j.jep.2017.08.011
PMID:28807849
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Danshen (Salvia miltiorrhiza Bunge) is widely used in traditional Chinese medicine. However, it's definite clinical effect and mechanism on colon carcinoma is unclear.

AIM OF THE STUDY

To test the hypothesis that the protective effect of danshen on colon cancer and discover the bioactive compounds through in vitro study.

MATERIALS AND METHODS

We conducted a nationwide cohort study by using population-based data from the Taiwan National Health Insurance Research Database (NHIRD). The study cohort comprised patients diagnosed with malignant neoplasm of colon (ICD-9-CM codes:153) in catastrophic illness database between January 1, 2000, and December 31, 2010. We used the Kaplan-Meier method to estimate colon [corrected] cancer cumulative incidences. Next, human colon cancer cells (HCT 116 cells and HT29 cells) were used to investigate the effect of dihydroisotanshinone I (DT) on the proliferation and apoptosis of human colon cancer cells and the underlying mechanism through XTT assay and flow cytometry. The in vivo effect of DT treatment was investigated through a xenograft nude mouse model.

RESULTS

In our study, the in vivo protective effect of danshen in the different stage of colon cancer patients was validated through data from the National Health Insurance Research Database in Taiwan. In vitro, we found that dihydroisotanshinone I (DT), a bioactive compound present in danshen, can inhibit the proliferation of colon carcinoma cells, HCT 116 cells and HT-29 cells. Moreover, DT induced apoptosis of colorectal cancer cells. DT also repressed the protein expression of Skp2 (S-Phase Kinase Associated Protein 2) and the mRNA levels of its related gene, Snail1 (Zinc finger protein SNAI1) and RhoA (Ras homolog gene family, member A). In addition, DT also blocked the colon cancer cells recruitment ability of macrophage by decreasing CCL2 secretion in macrophages. DT treatment also significantly inhibited the final tumor volume in a xenograft nude mouse model.

CONCLUSION

Danshen has protective effects in colon cancer patients, which could be attributed to DT through blocking the proliferation of colon cancer cells through apoptosis.

摘要

民族药理学相关性

丹参(丹参)广泛用于中药。然而,它对结肠癌的确切临床效果和机制尚不清楚。

研究目的

通过体外研究检验丹参对结肠癌的保护作用假设,并发现生物活性化合物。

材料与方法

我们通过使用来自台湾全民健康保险研究数据库(NHIRD)的基于人群的数据进行了全国范围的队列研究。该研究队列包括 2000 年 1 月 1 日至 2010 年 12 月 31 日在灾难性疾病数据库中诊断患有结肠癌(ICD-9-CM 代码:153)的患者。我们使用 Kaplan-Meier 方法估计结肠癌[更正]癌症累积发生率。接下来,用人结肠癌细胞(HCT 116 细胞和 HT29 细胞)研究二氢异丹参酮 I(DT)对人结肠癌细胞增殖和凋亡的影响及其通过 XTT 测定和流式细胞术的潜在机制。通过异种移植裸鼠模型研究 DT 治疗的体内作用。

结果

在我们的研究中,通过来自台湾全民健康保险研究数据库的数据验证了丹参在结肠癌不同阶段的体内保护作用。在体外,我们发现丹参中的生物活性化合物二氢异丹参酮 I(DT)可抑制结肠癌细胞、HCT 116 细胞和 HT-29 细胞的增殖。此外,DT 诱导结直肠癌细胞凋亡。DT 还抑制 Skp2(S 期激酶相关蛋白 2)的蛋白表达及其相关基因 Snail1(锌指蛋白 SNAI1)和 RhoA(Ras 同源基因家族,成员 A)的 mRNA 水平。此外,DT 还通过减少巨噬细胞中 CCL2 的分泌来阻断结肠癌细胞对巨噬细胞的募集能力。DT 治疗还显著抑制异种移植裸鼠模型中的最终肿瘤体积。

结论

丹参对结肠癌患者具有保护作用,这可能归因于 DT 通过凋亡抑制结肠癌细胞的增殖。

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