Akhtar Javed, Imran Muhammad, Wang Guanyu
Futian Biomedical Innovation R&D Center, The Chinese University of Hong Kong, Shenzhen 518172, China.
Biomedical Science and Engineering, School of Medicine, The Chinese University of Hong Kong, Shenzhen 518172, China.
Int J Mol Sci. 2023 Sep 13;24(18):14030. doi: 10.3390/ijms241814030.
Innovative therapeutic strategies for esophageal squamous cell carcinoma (ESCC) are urgently required due to the limited effectiveness of standard chemotherapies. C-Terminal Binding Protein 1 (CtBP1) has been implicated in various cancers, including ESCC. However, the precise expression patterns and functional roles of CtBP1 in ESCC remain inadequately characterized. In this study, we aimed to investigate CtBP1 expression and its role in the resistance of ESCC to paclitaxel, an effective chemotherapeutic agent. Western blotting and immunofluorescence were applied to assess CtBP1 expression in the TE-1 and KYSE-50 cell lines. We observed the marked expression of CtBP1, which was associated with enhanced proliferation, invasion, and metastasis in these cell lines. Further, we successfully generated paclitaxel resistant ESCC cell lines and conducted cell viability assays. We employed the CRISPR/Cas9 genome editing system to disable the CtBP1 gene in ESCC cell lines. Through the analysis of the drug dose-response curve, we assessed the sensitivity of these cell lines in different treatment groups. Remarkably, CtBP1-disabled cell lines displayed not only improved sensitivity but also a remarkable inhibition of proliferation, invasion, and metastasis. This demonstrates that CtBP1 may promote ESCC cell malignancy and confer paclitaxel resistance. In summary, our study opens a promising avenue for targeted therapies, revealing the potential of CtBP1 inhibition to enhance the effectiveness of paclitaxel treatment for the personalized management of ESCC.
由于标准化疗的有效性有限，食管癌鳞状细胞癌（ESCC）迫切需要创新的治疗策略。C末端结合蛋白1（CtBP1）已被证明与包括ESCC在内的多种癌症有关。然而，CtBP1在ESCC中的精确表达模式和功能作用仍未得到充分表征。在本研究中，我们旨在研究CtBP1的表达及其在ESCC对紫杉醇（一种有效的化疗药物）耐药性中的作用。应用蛋白质免疫印迹法和免疫荧光法评估TE-1和KYSE-50细胞系中CtBP1的表达。我们观察到CtBP1的显著表达，这与这些细胞系中增殖、侵袭和转移的增强有关。此外，我们成功构建了耐紫杉醇的ESCC细胞系并进行了细胞活力测定。我们使用CRISPR/Cas9基因组编辑系统使ESCC细胞系中的CtBP1基因失活。通过分析药物剂量反应曲线，我们评估了不同治疗组中这些细胞系的敏感性。值得注意的是，CtBP1失活的细胞系不仅显示出更高的敏感性，而且对增殖、侵袭和转移有显著抑制作用。这表明CtBP1可能促进ESCC细胞的恶性程度并赋予其紫杉醇耐药性。总之，我们的研究为靶向治疗开辟了一条有前景的途径，揭示了抑制CtBP1以提高紫杉醇治疗ESCC个性化管理有效性的潜力。
