Department Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P. R. China.
Clinical Laboratory, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P. R. China.
Am J Chin Med. 2020;48(3):703-718. doi: 10.1142/S0192415X20500354. Epub 2020 Apr 24.
Cinobufacini is a well-known Chinese medicine extracted from Venenum Bufonis, also called Chan Su. It has been used clinically for various cancers, including colon cancer. However, the function of Cinobufacini on colon cancer invasion and metastasis, and its underlying molecular mechanism, is still not clear. In this study, we investigated the function and mechanism of Cinobufacini on colon cancer invasion and metastasis both and studies. Human colon cancer cells were cultured. CCK assay was used to detect the effect of Cinobufacini on colon cancer cells proliferation. The invasion and migration abilities were observed by transwell assays, and the expression of invasion and migration related genes MMP2, MMP9, and epithelial-to-mesenchymal transition (EMT) relate genes were observed by Western blot assays. An orthotopic xenograft model in nude mice was established using colon cancer HCT116 cells, and the function of Cinobufacini on colon cancer invasion and metastasis were observed . We found Cinobufacini significantly inhibited colon cancer cell proliferation in a dose/time-dependent manner; the invasion and migration abilities of colon cancer were decreased after treated with Cinobufacini. The metastasis and EMT related genes MMP9, MMP2, N-cadherin and Snail were obviously down-regulated, while the expression of E-cadherin was up-regulated after treatment with Cinobufacini. The Wnt/-catenin signaling pathway related genes were observed using WB,and results show that the expression of -catenin, wnt3a, c-myc, cyclin D1, and MMP7 were all down-regulated after being treated with cinobufacini, while the expression of APC was up-regulated. studies of the volume and weight of orthotopic xenograft tumors showed significantly shrinkage in the Cinobufacini group compared to the control group. The enterocoelia and liver metastasis tumors were significantly decreased, and the expression of MMP9, MMP2, and -catenin were also down-regulated, while E-cadherin was up-regulated after the treatment with Cinobufacini. Our data proves that Cinobufacini can inhibit colon cancer invasion and metastasis both and ; the mechanism is related by suppressing the Wnt/-catenin signaling pathway and then inhibiting the EMT of CRC.
华蟾素是一种从蟾酥中提取的中药，又称蟾酥。它已被临床用于治疗各种癌症，包括结肠癌。然而，华蟾素对结肠癌侵袭和转移的作用及其潜在的分子机制尚不清楚。在这项研究中，我们通过体内和体外研究来研究华蟾素对结肠癌侵袭和转移的作用和机制。培养人结肠癌细胞。CCK 法检测华蟾素对结肠癌细胞增殖的影响。Transwell 法观察细胞的侵袭和迁移能力，Western blot 法观察侵袭和迁移相关基因 MMP2、MMP9 和上皮间质转化（EMT）相关基因的表达。用人结肠癌 HCT116 细胞建立裸鼠原位移植瘤模型，观察华蟾素对结肠癌侵袭和转移的作用。我们发现华蟾素呈剂量和时间依赖性地显著抑制结肠癌细胞的增殖；用华蟾素处理后，结肠癌的侵袭和迁移能力下降。转移和 EMT 相关基因 MMP9、MMP2、N-钙黏蛋白和 Snail 明显下调，而 E-钙黏蛋白表达上调。用 WB 观察 Wnt/-catenin 信号通路相关基因，结果表明华蟾素处理后，-catenin、wnt3a、c-myc、cyclin D1 和 MMP7 的表达均下调，而 APC 的表达上调。对原位移植瘤体积和重量的研究表明，与对照组相比，华蟾素组明显缩小。腹腔和肝脏转移瘤明显减少，MMP9、MMP2 和 -catenin 的表达下调，E-钙黏蛋白表达上调。我们的数据证明华蟾素可以通过抑制 Wnt/-catenin 信号通路和抑制 CRC 的 EMT 来抑制结肠癌的侵袭和转移。
