a Institute of Hematology , Union Hospital, Tongji Medical College, Huazhong University of Science & Technology , Wuhan , China.
b School of Pharmacy , Fudan University, Key Laboratory of Smart Drug Delivery, Ministry of Education , Shanghai , China.
J Drug Target. 2018 Dec;26(10):913-919. doi: 10.1080/1061186X.2018.1452243. Epub 2018 Mar 20.
As one of the most intractable tumours, pancreatic ductal adenocarcinoma (PDA) has a dense extracellular matrix (ECM) which could increase solid stress within tumours to compress tumour vessels, reduce tumour perfusion and compromise nanomedicine delivery for PDA. Thus, alleviating solid stress represents a potential therapeutic target for PDA treatment. In this study, cyclopamine, a special inhibitor of the hedgehog signalling pathway which contributes a lot to ECM formation of PDA, was exploited to alleviate solid stress and improve nanomedicine delivery to PDA. Results demonstrated that cyclopamine successfully disrupted ECM and lowered solid stress within PDA, which increased functional tumour vessels and resulted in enhanced tumour perfusion as well as improved tumour nanomedicine delivery in PDA-bearing animal models. Therefore, solid stress within PDA represents a new therapeutic target for PDA treatment.
作为最棘手的肿瘤之一，胰腺导管腺癌（PDA）具有密集的细胞外基质（ECM），这会增加肿瘤内的固有力，从而压迫肿瘤血管，减少肿瘤灌注，并影响 PDA 的纳米药物递送。因此，缓解固有力代表了治疗 PDA 的一个潜在治疗靶点。在这项研究中，使用了 Hedgehog 信号通路的特殊抑制剂——鲨烯，这对 PDA 的 ECM 形成有很大的作用，以缓解固有力并改善 PDA 的纳米药物递送。结果表明，鲨烯成功地破坏了 PDA 中的 ECM 并降低了固有力，增加了功能性肿瘤血管，从而增强了肿瘤灌注，并改善了 PDA 荷瘤动物模型中的肿瘤纳米药物递送。因此，PDA 内的固有力代表了治疗 PDA 的一个新的治疗靶点。
