CTI-2 inhibits metastasis and epithelial-mesenchymal transition of breast cancer cells by modulating MAPK signaling pathway. CTI-2 inhibits metastasis and epithelial-mesenchymal transition of breast cancer cells by modulating MAPK signaling pathway

Although some breast cancer patients die due to tumor metastasis rather than from the primary tumor, the molecular mechanism of metastasis remains unclear. Therefore, it is necessary to inhibit breast cancer metastasis during cancer treatment. In this case, after designing and synthesizing CTI-2, we found that CTI-2 treatment significantly reduced breast cancer cell metastasis in vivo and in vitro. Notably, with the treatment of CTI-2 in breast cancer cells, the expression level of E-cadherin increased, while the expression level of N-cadherin and vimentin decreased. In addition, after CTI-2 treatment, those outflow levels for p-ERK, p-p38, and p-JNK diminished, while no significant changes in the expression levels of ERK, JNK, or p38 were observed. Our conclusion suggested that CTI-2 inhibits the epithelial-mesenchymal transition (EMT) of breast carcinoma cells by inhibiting the activation of the mitogen-activated protein kinase (MAPK) signaling pathway, thereby inhibiting the metastasis of breast tumor cells. Therefore, we believe that CTI-2 is another candidate for breast tumor medication. Overall design: The mRNA profile of MDA-MB-231 cells treated with or without CTI-2 for 24 hours

虽然部分乳腺癌患者死于肿瘤转移而非原发肿瘤，但转移的分子机制仍未明确。因此在癌症治疗过程中抑制乳腺癌转移具有重要意义。本研究中，我们设计并合成了CTI-2，后续实验发现CTI-2处理可显著降低体内外乳腺癌细胞的转移能力。值得注意的是，经CTI-2处理的乳腺癌细胞中，E-钙粘蛋白（E-cadherin）的表达水平显著升高，而N-钙粘蛋白（N-cadherin）与波形蛋白（vimentin）的表达水平则出现下降。此外，经CTI-2处理后，p-ERK、p-p38及p-JNK的磷酸化水平显著降低，而ERK、JNK及p38的总蛋白表达水平未观察到明显变化。本研究结论表明，CTI-2可通过抑制丝裂原活化蛋白激酶（mitogen-activated protein kinase, MAPK）信号通路的激活，阻断乳腺癌细胞的上皮间质转化（epithelial-mesenchymal transition, EMT），进而抑制乳腺肿瘤细胞的转移。因此，我们认为CTI-2可作为乳腺肿瘤治疗药物的候选化合物之一。总体实验设计：将MDA-MB-231细胞分为CTI-2处理组与对照组，分别经CTI-2处理或不经处理培养24小时后，提取细胞mRNA进行表达谱分析。