pancreatic cancer treatment with L-Asparaginase

Pancreatic cancer has a poor prognosis due to limited therapeutic options. Accumulating evidence has revealed the cancer therapeutic effects of L-Asparaginase, one of the most commonly used drugs for leukemia and lymphoma. However, its role in pancreatic cancer is not fully elucidated. Herein, our study showed that L-Asparaginase inhibited cell proliferation and activated ROS accumulation to induced apoptosis of pancreatic cancer cells. Meanwhile, L-Asparaginase significantly suppressed the migration and invasion of pancreatic cancer cells and reduced the expression of epithelial-mesenchymal transition (EMT) related proteins. Further, L-Asparaginase profoundly inhibits pancreatic cancer cell growth in vivo. Mechanistically, RNA transcriptome sequence analysis (RNA-Seq) revealed that L-Asparaginase exerted the anti-tumor effect by activating the Hippo signaling pathway. Therefore, our research provided the rationale for further clinical evaluation of L-Asparaginase as a therapeutic agent in treating pancreatic cancer.

胰腺癌因治疗手段有限，预后极差。越来越多的研究证据表明，L-天冬酰胺酶（L-Asparaginase）——一种白血病与淋巴瘤临床常用药物——具有抗肿瘤治疗效应。然而，其在胰腺癌中的作用尚未完全阐明。本研究发现，L-天冬酰胺酶可抑制胰腺癌细胞增殖，通过激活活性氧（ROS）积累诱导癌细胞凋亡；同时可显著抑制胰腺癌细胞的迁移与侵袭能力，并下调上皮间质转化（EMT）相关蛋白的表达。进一步实验证实，L-天冬酰胺酶在体内可显著抑制胰腺癌细胞的生长。机制研究显示，RNA转录组测序分析（RNA-Seq）结果表明，L-天冬酰胺酶通过激活Hippo信号通路发挥抗肿瘤作用。综上，本研究为L-天冬酰胺酶作为治疗药物应用于胰腺癌的后续临床评估提供了理论依据。