The acquisition of chemoresistance is a major clinical challenge for pancreatic cancer (PC) treatment. Chemoresistance is largely attributed to aberrant DNA damage repair. However, the underlying mechanisms of chemoresistance in pancreatic cancer remain unclear. Here, we showed that CD147 was strongly correlated to DNA damage response (DDR) indices and poor prognosis in pancreatic ductal adenocarcinoma (PDAC) patients. CD147 knockdown or monoclonal antibodies improved the killing effects of gemcitabine in gemcitabine resistant cells, exhibiting reduced activation of ATM/p53.

Moreover, we found the interaction of CD147 with ATM, ATR and p53, which was augmented in gemcitabine resistant cells. High CD147/p-ATM/p-ATR/p-p53 cytoplasmic expression associated with poor survival of PC patients. Our studies thus identify CD147 as a critical player in DDR programing that affects gemcitabine therapeutic outcomes of pancreatic cancer patients.

化学抗性的获得是胰腺癌（PC）治疗的主要临床挑战。化学抗性在很大程度上归因于异常的DNA损伤修复。然而，胰腺癌化学耐药的潜在机制仍不清楚。在这里，我们显示了CD147与胰腺导管腺癌（PDAC）患者的DNA损伤反应（DDR）指数和不良预后密切相关。CD147组合式或单克隆抗体改善了吉西他滨耐药细胞中吉西他滨的杀伤作用，显示出ATM / p53的激活减少。

此外，我们发现CD147与ATM，ATR和p53的相互作用在吉西他滨耐药细胞中得到增强。高CD147 / p-ATM / p-ATR / p-p53细胞质表达与PC患者生存不良有关。因此，我们的研究确定CD147是DDR编程的关键参与者，该编程会影响吉西他滨对胰腺癌患者的治疗效果。