Xu Liang, Sun Jing, Guo Junlan, Guo Shengnan, Li Jiangli, Tang Yijun, Liu Xiaohui
Department of Medical Oncology, Anyang Cancer Hospital, Anyang, China.
J Chemother. 2024 Nov 3:1-12. doi: 10.1080/1120009X.2024.2421701.
The emergence of resistance to 5-Fluorouracil (5-FU) is a staple in breast cancer chemotherapy. This paper delves into the role of PTEN in breast cancer resistance to 5-FU and examines the underlying molecular pathways. PTEN expression was detected in bioinformatics databases and upstream transcription factors (TFs) were identified. PTEN mRNA and protein levels, aerobic glycolysis proteins, lactate production, glucose consumption, and cell viability were measured. Binding interactions were confirmed, and cell proliferation assessed. In breast cancer cells, PTEN expression was downregulated. PTEN overexpression counteracted 5-FU resistance through the suppression of aerobic glycolysis. KLF9, as a TF upstream of PTEN, enhanced the levels of PTEN. In conclusion, the TF KLF9 inhibits the aerobic glycolysis level of breast cancer cells by up-regulating PTEN expression, thereby reducing their resistance to 5-FU. The discovery of this mechanism provides a new theoretical basis for the treatment of breast cancer.
对5-氟尿嘧啶（5-FU）产生耐药性是乳腺癌化疗中的常见问题。本文深入探讨了PTEN在乳腺癌对5-FU耐药中的作用，并研究了其潜在的分子途径。在生物信息学数据库中检测PTEN表达，并鉴定上游转录因子（TFs）。测量PTEN mRNA和蛋白水平、有氧糖酵解蛋白、乳酸生成、葡萄糖消耗和细胞活力。确认结合相互作用，并评估细胞增殖。在乳腺癌细胞中，PTEN表达下调。PTEN过表达通过抑制有氧糖酵解抵消了5-FU耐药性。作为PTEN上游的转录因子，KLF9提高了PTEN的水平。总之，转录因子KLF9通过上调PTEN表达抑制乳腺癌细胞的有氧糖酵解水平，从而降低其对5-FU的耐药性。这一机制的发现为乳腺癌治疗提供了新的理论依据。
