Zhang Ruijie, Li Shengjin, Lan Jian, Li Changyi, Du Xianzhi, Dong Weijie, Yu Qian, Wang Daoxin
Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Front Genet. 2022 May 27;13:891665. doi: 10.3389/fgene.2022.891665. eCollection 2022.
Tumor metastasis and invasion are the main impediments to lung adenocarcinoma successful treatment. Previous studies demonstrate that chemotherapeutic agents can elevate the malignancy of cancer cells other than their therapeutic effects. In this study, the effects of transient low-dose cisplatin treatment on the malignant development of lung adenocarcinoma cells (A549) were detected, and the underlying epigenetic mechanisms were investigated. The findings showed that A549 cells exhibited epithelial-mesenchymal transition (EMT)-like phenotype along with malignant progression under the transient low-dose cisplatin treatment. Meanwhile, low-dose cisplatin was found to induce contactin-1 () upregulation in A549 cells. Subsequently, we found that further overexpressing -1 in A549 cells obviously activated the EMT process and , and caused malignant development of A549 cells . Taken together, we conclude that low-dose cisplatin can activate the EMT process and resulting malignant progression through upregulating in A549 cells. The findings provided new evidence that a low concentration of chemotherapeutic agents could facilitate the malignancy of carcinoma cells activating the EMT process other than their therapeutic effects.
肿瘤转移和侵袭是肺腺癌成功治疗的主要障碍。先前的研究表明，化疗药物除了具有治疗作用外，还会提高癌细胞的恶性程度。在本研究中，检测了短暂低剂量顺铂处理对肺腺癌细胞（A549）恶性进展的影响，并研究了其潜在的表观遗传机制。结果显示，在短暂低剂量顺铂处理下，A549细胞呈现出上皮-间质转化（EMT）样表型并伴有恶性进展。同时，发现低剂量顺铂可诱导A549细胞中接触蛋白-1（）上调。随后，我们发现进一步在A549细胞中过表达-1明显激活了EMT过程并，导致A549细胞恶性进展。综上所述，我们得出结论，低剂量顺铂可通过上调A549细胞中的来激活EMT过程并导致恶性进展。这些发现提供了新的证据，即低浓度化疗药物除了具有治疗作用外，还可通过激活EMT过程促进癌细胞的恶性程度。
