Abnormal expression of ACSL members 1, 3, 4, 5, and 6 is frequently seen in human cancer; however, their clinical relevance is unclear. In this study, we analyzed the expression of ACSLs and investigated the effects of the ACSL inhibitor Triacsin C (TC) in lung cancer. We found that, compared to normal human bronchial epithelial (NHBE) cells, ACSL1, ACSL4, and ACSL6 were highly expressed, while ACSL3 and ACSL5 were lost in the majority of lung cancer cell lines. ACSL activity was associated with the expression levels of the ACSLs. In primary lung tumors, a higher expression of ACSL1, ACSL4, and ACSL5 was significantly correlated with adenocarcinoma (ADC). Moreover, ACSL5 was significantly reversely related to the proliferation marker Ki67 in low-grade tumors, while ACSL3 was positively associated with Ki67 in high-grade tumors. Combination therapy with TC and Gemcitabine enhanced the growth-inhibitory effect in EGFR wild-type cells, while TC combined with EGFR-TKIs sensitized the EGFR-mutant cells to EGFR-TKI treatment. Taken together, the data suggest that ACSL1 may be a biomarker for lung ADC, and ACSL1, ACSL4, and ACSL5 may be involved in lung cancer differentiation, and TC, in combination with chemotherapy or EGFR-TKIs, may help patients overcome drug resistance.
ACSL家族成员1、3、4、5、6的异常表达常见于人类癌症，但其临床意义尚不明确。本研究分析了ACSLs在肺癌中的表达情况，并探讨了ACSL抑制剂Triacsin C（TC）的作用机制。研究发现，与正常人支气管上皮（NHBE）细胞相比，多数肺癌细胞系中ACSL1、ACSL4和ACSL6呈高表达，而ACSL3和ACSL5表达缺失。ACSL活性与其表达水平呈正相关。在原发肺肿瘤中，ACSL1、ACSL4和ACSL5的高表达与肺腺癌（ADC）显著相关。值得注意的是，在低级别肿瘤中ACSL5与增殖标志物Ki67呈显著负相关，而在高级别肿瘤中ACSL3与Ki67呈正相关。联合用药实验表明，TC与吉西他滨联用可增强对EGFR野生型细胞的生长抑制作用，而TC与EGFR-TKIs联用则能提高EGFR突变细胞对EGFR-TKI治疗的敏感性。综上所述，ACSL1可能作为肺腺癌的生物标志物，ACSL1、ACSL4和ACSL5可能参与肺癌分化进程，而TC与化疗药物或EGFR-TKIs的联合应用或有助于患者克服耐药性问题。
肿瘤(癌症)患者之家