Liu Yang, Li Fan, Gao Feng, Xing Lingxi, Qin Peng, Liang Xingxin, Zhang Jiajie, Qiao Xiaohui, Lin Lizhou, Zhao Qian, Du Lianfang
Department of Ultrasound, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200080, China.
Department of Instrument Science and Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China.
Tumour Biol. 2016 Nov;37(11):15283-15291. doi: 10.1007/s13277-016-5321-6. Epub 2016 Sep 30.
Pancreatic ductal adenocarcinoma (PDAC) ranks fourth among cancer-related deaths. The nucleoside analog gemcitabine has been the cornerstone of adjuvant chemotherapy in PDAC for decades. However, gemcitabine resistance develops within weeks of chemotherapy initiation, which might be intrinsic to cancer cells and influenced by tumor microenvironment. Recently, pancreatic stellate cells (PSCs) have greatly increased our attention on tumor microenvironment-mediated drug resistance. Periostin is exclusively overexpressed in PSCs and the stroma of PDAC creating a tumor-supportive microenvironment in the pancreas. However, whether periostin contributed to chemoresistance in PDAC remains unknown. Therefore, we focused on the role of periostin in PDAC by observing the effects of silencing this gene on gemcitabine resistance in vitro and in vivo aiming to explore the possible molecular mechanism. In this study, the pancreatic cancer cell (PCC) proliferation and apoptosis were assayed to investigate the sensitivity to gemcitabine after silencing periostin. We provide the evidence that periostin not only drives the carcinogenic process itself but also significantly associated with gemcitabine-induced apoptosis. These findings collectively indicated that periostin increases the chemoresistance to gemcitabine. Thus, targeting periostin might offer a new opportunity to overcome the gemcitabine resistance of PDAC.
胰腺导管腺癌（PDAC）在癌症相关死亡原因中位列第四。几十年来，核苷类似物吉西他滨一直是PDAC辅助化疗的基石。然而，化疗开始数周内就会出现吉西他滨耐药，这可能是癌细胞固有的，且受肿瘤微环境影响。最近，胰腺星状细胞（PSC）极大地提高了我们对肿瘤微环境介导的耐药性的关注。骨膜蛋白仅在PSC和PDAC的基质中过度表达，在胰腺中形成一个支持肿瘤的微环境。然而，骨膜蛋白是否导致PDAC的化疗耐药仍不清楚。因此，我们通过观察沉默该基因对体外和体内吉西他滨耐药性的影响，聚焦于骨膜蛋白在PDAC中的作用，旨在探索可能的分子机制。在本研究中，检测胰腺癌细胞（PCC）的增殖和凋亡，以研究沉默骨膜蛋白后对吉西他滨的敏感性。我们提供的证据表明，骨膜蛋白不仅驱动致癌过程本身，还与吉西他滨诱导的凋亡显著相关。这些发现共同表明，骨膜蛋白增加了对吉西他滨的化疗耐药性。因此，靶向骨膜蛋白可能为克服PDAC的吉西他滨耐药性提供新的机会。
