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片仔癀抑制结肠癌细胞中的干细胞样侧群细胞。

Pien Tze Huang suppresses the stem-like side population in colorectal cancer cells.

作者信息

Wei Lihui, Chen Pangyu, Chen Youqin, Shen Aling, Chen Hongwei, Lin Wei, Hong Zhenfeng, Sferra Thomas J, Peng Jun

机构信息

Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, P.R. China.

出版信息

Mol Med Rep. 2014 Jan;9(1):261-6. doi: 10.3892/mmr.2013.1760. Epub 2013 Oct 29.

Abstract

Accumulating evidence suggests that a small population of cells termed cancer stem cells (CSCs) are crucial in tumor development and drug resistance, leading to cancer relapse and metastasis and eventually the failure of clinical cancer treatment. Therefore, targeting CSCs is a promising approach for anticancer therapies. Due to the drug resistance and adverse effects of currently used chemotherapies, traditional Chinese medicines (TCM) have recently received attention due to the relatively few side-effects. Thus, they have been used as important alternative remedies for various diseases, including cancer. Pien Tze Huang (PZH), a well-known TCM formula that was first prescribed more than 450 years ago in the Ming Dynasty, has been used in China and Southeast Asia for centuries as a folk remedy for various types of cancer. Previously, it was reported that PZH inhibits colon cancer growth via the promotion of cancer cell apoptosis and inhibition of cell proliferation and tumor angiogenesis, which is probably mediated by its regulatory effect on multiple intracellular signaling pathways. To elucidate the mechanism of the tumoricidal activity of PZH, the aim of the present study was to investigate the effect of PZH on CSCs that were isolated as the side population (SP) from the HT-29 colorectal cancer cell line. The results demonstrated that PZH significantly and dose-dependently reduced the percentage of the colorectal cancer stem-like SP cells, decreased the viability and sphere-forming capacity of HT-29 SP cells, indicating that PZH is potent in suppressing the growth of colorectal cancer stem cells. Moreover, PZH treatment in HT-29 SP cells markedly inhibited the mRNA levels of ABCB1 and ABCG2, which are members of the ABC transporter superfamily, thereby contributing to the SP phenotype and multi-drug resistance. Findings of the present study suggest that inhibiting the growth of CSCs is a potential mechanism by which PZH can be used in cancer treatment.

摘要

越来越多的证据表明,一小部分被称为癌症干细胞(CSCs)的细胞在肿瘤发展和耐药性中起着关键作用,导致癌症复发和转移,最终导致临床癌症治疗失败。因此,靶向癌症干细胞是一种很有前景的抗癌治疗方法。由于目前使用的化疗药物存在耐药性和副作用,传统中药(TCM)因其副作用相对较少,最近受到了关注。因此,它们已被用作包括癌症在内的各种疾病的重要替代疗法。片仔癀(PZH)是一种著名的中药配方,早在450多年前的明朝就已被开方使用,在中国和东南亚已经作为治疗各种癌症的民间药物使用了几个世纪。此前有报道称,片仔癀通过促进癌细胞凋亡、抑制细胞增殖和肿瘤血管生成来抑制结肠癌生长,这可能是由其对多种细胞内信号通路的调节作用介导的。为了阐明片仔癀的杀瘤活性机制,本研究的目的是研究片仔癀对从HT-29结肠癌细胞系中分离出的作为侧群(SP)的癌症干细胞的影响。结果表明,片仔癀显著且剂量依赖性地降低了结肠直肠癌干细胞样SP细胞的百分比,降低了HT-29 SP细胞的活力和球形成能力,表明片仔癀在抑制结肠直肠癌干细胞生长方面具有效力。此外,对HT-29 SP细胞进行片仔癀处理显著抑制了ABCB1和ABCG2的mRNA水平,它们是ABC转运蛋白超家族的成员,从而导致SP表型和多药耐药性。本研究结果表明,抑制癌症干细胞的生长是片仔癀可用于癌症治疗的潜在机制。

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