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利用患者来源的肿瘤异种移植模型评估BP3B对结肠癌的抗肿瘤活性。

Evaluation of anti-tumorigenic activity of BP3B against colon cancer with patient-derived tumor xenograft model.

作者信息

Kim Hye-Youn, Kim Jinhee, Ha Thi Huyen Trang, Bang Ok-Sun, Lee Won-Suk, Hong Suntaek

机构信息

Department of Biochemistry, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, 155 Gaetbel-ro Yeonsu-gu, Incheon, 21999, Republic of Korea.

KM-Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon, 34054, Republic of Korea.

出版信息

BMC Complement Altern Med. 2016 Nov 18;16(1):473. doi: 10.1186/s12906-016-1447-8.

Abstract

BACKGROUND

KIOM-CRC#BP3B (BP3B) is a novel herbal prescription that is composed of three plant extracts. Our preliminary study identified that BP3B exhibited potent anti-proliferative activity against various types of cancer cell lines in vitro. Because the in vivo anti-tumor effect of BP3B is not evaluated before clinical trial, we want to test it using patient's samples.

METHODS

To confirm the in vivo anti-cancer effect of BP3B, we used genetically characterized patient-derived colon tumor xenograft (PDTX) mouse model. Anti-cancer activity was evaluated with apoptosis, proliferation, angiogenesis and histological analysis.

RESULTS

Oral administration of BP3B significantly inhibited the tumor growth in two PDTX models. Furthermore, TUNEL assay showed that BP3B induced apoptosis of tumor tissues, which was associated with degradation of PARP and Caspase 8 and activation of Caspase 3. We also observed that BP3B inhibited cancer cell proliferation by down-regulation of Cyclin D1 and induction of p27 proteins. Inhibition of angiogenesis in BP3B-treated group was observed with immunofluorescence staining using CD31 and Tie-2 antibodies.

CONCLUSION

These findings indicated that BP3B has a strong growth-inhibitory activity against colon cancer in in vivo model and will be a good therapeutic candidate for treatment of refractory colon cancer.

摘要

背景

KIOM-CRC#BP3B(BP3B)是一种由三种植物提取物组成的新型草药配方。我们的初步研究发现,BP3B在体外对多种癌细胞系表现出强大的抗增殖活性。由于在临床试验前未评估BP3B的体内抗肿瘤作用,我们想用患者样本进行测试。

方法

为了证实BP3B的体内抗癌作用,我们使用了基因特征明确的患者来源的结肠肿瘤异种移植(PDTX)小鼠模型。通过凋亡、增殖、血管生成和组织学分析评估抗癌活性。

结果

口服BP3B显著抑制了两种PDTX模型中的肿瘤生长。此外,TUNEL检测表明BP3B诱导肿瘤组织凋亡,这与PARP和Caspase 8的降解以及Caspase 3的激活有关。我们还观察到BP3B通过下调Cyclin D1和诱导p27蛋白来抑制癌细胞增殖。使用CD31和Tie-2抗体进行免疫荧光染色观察到BP3B治疗组的血管生成受到抑制。

结论

这些发现表明BP3B在体内模型中对结肠癌具有强大的生长抑制活性,将是治疗难治性结肠癌的良好候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab9d/5116142/1fd5fb42e5f4/12906_2016_1447_Fig1_HTML.jpg

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