a Department of Pharmaceutical Engineering , Beijing Institute of Petrochemical Technology , Beijing , China and.
b School of Pharmacy , Liaoning University of Traditional Chinese Medicine , Dalian , China.
J Liposome Res. 2018 Sep;28(3):236-248. doi: 10.1080/08982104.2017.1327542. Epub 2017 May 24.
Non-small cell lung carcinoma (NSCLC) is a type of epithelial lung cancer that accounts for approximately 80-85% of lung carcinoma cases. Chemotherapy for the NSCLC is unsatisfactory due to multidrug resistance, nonselectively distributions and the accompanying side effects.
The objective of this study was to develop a kind of PTD modified paclitaxel anti-resistant liposomes to overcome these chemotherapy limitations.
The studies were performed on LLT cells and resistant LLT cells in vitro and on NSCLC xenograft mice in vivo, respectively.
In vitro results showed that the liposomes with suitable physicochemical characteristics could significantly increase intracellular uptake in both LLT cells and resistant LLT cells, evidently inhibit the growth of cancer cells, and clearly induce the apoptosis of resistant LLT cells. Studies on resistant LLT cells xenograft mice demonstrated that the liposomes magnificently enhanced the anticancer efficacy in vivo. Involved action mechanisms were down-regulation of adenosine triphosphate binding cassette transporters on resistant LLT cells, and activation of the apoptotic enzymes (caspase 8/9/3).
The PTD modified paclitaxel anti-resistant liposomes may provide a promising strategy for treatment of the drug-resistant non-small cell lung cancer.
非小细胞肺癌（NSCLC）是一种上皮性肺癌，约占肺癌病例的 80-85%。由于多药耐药性、非选择性分布以及伴随的副作用，NSCLC 的化疗效果并不理想。
本研究旨在开发一种 PTD 修饰的紫杉醇抗耐药脂质体，以克服这些化疗限制。
分别在体外的 LLT 细胞和耐药 LLT 细胞以及体内的 NSCLC 异种移植小鼠上进行了这些研究。
体外结果表明，具有合适理化特性的脂质体能够显著增加 LLT 细胞和耐药 LLT 细胞的细胞内摄取，明显抑制癌细胞的生长，并明显诱导耐药 LLT 细胞的凋亡。在耐药 LLT 细胞异种移植小鼠上的研究表明，脂质体在体内显著增强了抗癌疗效。涉及的作用机制是下调耐药 LLT 细胞上的三磷酸腺苷结合盒转运蛋白，并激活凋亡酶（半胱天冬酶 8/9/3）。
PTD 修饰的紫杉醇抗耐药脂质体可能为治疗耐药性非小细胞肺癌提供了一种有前途的策略。
