Abstract：
Lung cancer is one of the most fatal cancers worldwide. Resistance to conventional therapies remains a hindrance to patient treatment. Therefore, the development of more effective anti-cancer therapeutic strategies is imperative. Solid tumors exhibit a hyperglycolytic phenotype, leading to enhanced lactate production; and, consequently, its extrusion to the tumor microenvironment. Previous data reveals that inhibition of CD147, the chaperone of lactate transporters (MCTs), decreases lactate export in lung cancer cells and sensitizes them to phenformin, leading to a drastic decrease in cell growth. In this study, the development of anti-CD147 targeted liposomes (LUVs) carrying phenformin is envisioned, and their efficacy is evaluated to eliminate lung cancer cells. Herein, the therapeutic effect of free phenformin and anti-CD147 antibody, as well as the efficacy of anti-CD147 LUVs carrying phenformin on A549, H292, and PC-9 cell growth, metabolism, and invasion, are evaluated. Data reveals that phenformin decreases 2D and 3D-cancer cell growth and that the anti-CD147 antibody reduces cell invasion. Importantly, anti-CD147 LUVs carrying phenformin are internalized by cancer cells and impaired lung cancer cell growth in vitro and in vivo. Overall, these results provide evidence for the effectiveness of anti-CD147 LUVs carrying phenformin in compromising lung cancer cell aggressiveness.
摘要：
肺癌是全球最致命的癌症之一。对常规疗法的抗性仍然是患者治疗的障碍。因此,开发更有效的抗癌治疗策略势在必行.实体瘤表现出高糖酵解表型，导致乳酸产量增加；以及，因此,它对肿瘤微环境的挤压。以前的数据表明，抑制CD147，乳酸转运蛋白（MCT）的伴侣，减少肺癌细胞中的乳酸输出，并使其对苯乙双胍敏感，导致细胞生长急剧下降。在这项研究中,设想了携带苯乙双胍的抗CD147靶向脂质体（LUVs）的开发，并评估其消除肺癌细胞的功效。在这里，游离苯乙双胍和抗CD147抗体的治疗效果，以及携带苯乙双胍的抗CD147LUVs对A549，H292和PC-9细胞生长的功效，新陈代谢，和入侵,进行了评估。数据显示,苯乙双胍降低2D和3D癌细胞生长,并且抗CD147抗体降低细胞侵袭。重要的是,携带苯乙双胍的抗CD147LUVs被癌细胞内化，并在体外和体内受损的肺癌细胞生长。总的来说,这些结果为携带苯乙双胍的抗CD147LUVs在降低肺癌细胞侵袭性方面的有效性提供了证据.
