Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India.
Centre for Chemical Biology, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India; School of Chemical & Biotechnology, SASTRA University, Tirumalaisamudram, Thanjavur 613401, India.
Life Sci. 2016 Apr 15;151:264-276. doi: 10.1016/j.lfs.2016.03.024. Epub 2016 Mar 12.
Breast cancer is highly resistant to chemotherapeutic approach and hence, alternative strategies have been developed to fight against this heterogeneous group of disease. In particular, many studies have demonstrated about various drugs for the treatment of breast cancer. In our study, we assessed the anti-angiogenenic activities of Bisindole-PBD (5b) in MCF-7 and MDA-MB-231 cell lines.
In vitro Endothelial Cell (HUVEC) Tube Formation Assay was performed to show inhibitory role of 5b along with its role upon wound healing process in breast cancer cells in vitro. Semi-quantitative reverse transcription PCR (RT-PCR) was also done to examine the expression of VEGF in response to 5b in breast cancer cells and in HUVEC cells. siRNA transfection study explored STAT3 mediated VEGF transcription in breast cancer cells MCF-7 and MDA-MB-231. CAM assay was performed to see the role of 5b on vessel formation in chicken embryo.
From in vitro data we have demonstrated that 5b played a role in regulation of breast cancer cell proliferation by inhibiting angiogenesis. Test drug 5b suppressed the expression VEGF at both transcriptional and post transcriptional levels. Apart from this, there was significant down regulation in STAT3 level after drug treatment, which was found to be involved in the VEGF transcription. Metastasis related MMP-2 and MMP-9 expressions were also modulated by 5b. In vivo study by Chick Chorioallantoic Membrane (CAM) Assay also showed anti-angiogenesis role of the test drug which was consistent with the in vitro data.
Altogether, our data demonstrated 5b as potent small molecule with anti-angiogenic activities.
乳腺癌对化疗方法具有高度抗性，因此开发了替代策略来对抗这种异质疾病群体。特别是，许多研究已经证明了许多用于治疗乳腺癌的药物。在我们的研究中，我们评估了双吲哚-PBD（5b）在 MCF-7 和 MDA-MB-231 细胞系中的抗血管生成活性。
进行体外内皮细胞（HUVEC）管形成测定，以显示 5b 在体外乳腺癌细胞中的伤口愈合过程中抑制作用及其作用。还进行了半定量逆转录 PCR（RT-PCR），以检查 5b 对乳腺癌细胞和 HUVEC 细胞中 VEGF 表达的影响。siRNA 转染研究探索了 STAT3 在 MCF-7 和 MDA-MB-231 乳腺癌细胞中介导的 VEGF 转录。CAM 测定用于观察 5b 在鸡胚中的血管形成中的作用。
从体外数据我们已经证明，5b 通过抑制血管生成在调节乳腺癌细胞增殖中发挥作用。测试药物 5b 在转录和转录后水平上抑制 VEGF 的表达。除此之外，药物治疗后 STAT3 水平显著下调，这被发现涉及 VEGF 转录。转移相关的 MMP-2 和 MMP-9 表达也被 5b 调节。体内研究通过鸡绒毛尿囊膜（CAM）测定也显示了测试药物的抗血管生成作用，这与体外数据一致。
总之，我们的数据表明 5b 是一种具有抗血管生成活性的有效小分子。
