Gadzinski Jill A, Guo Jianxia, Philips Brian J, Basse Per, Craig Ethan K, Bailey Lisa, Comerci John T, Eiseman Julie L
Magee Women's Hospital of the University of Pittsburgh, Department of Obstetrics/Gynecology/Reproductive Sciences, 300 Halket Street, Pittsburgh, USA, 15213.
Cancer Therapeutics Program, University of Pittsburgh Cancer Institute, and Department of Pharmacology and Chemical Biology, School of Medicine, University of Pittsburgh, 5117 Centre Ave., Pittsburgh, PA 15213.
Adv Biol Chem. 2016 Dec;6(6):193-215. doi: 10.4236/abc.2016.66017. Epub 2016 Dec 30.
Cervical cancer is the second most common cancer in women worldwide [1]. Photodynamic therapy has been used for cervical intraepithelial neoplasia with good responses, but few studies have used newer phototherapeutics. We evaluated the effectiveness of photodynamic therapy using Pc 4 in vitro and in vivo against human cervical cancer cells.
CaSki and ME-180 cancer cells were grown as monolayers and spheroids. Cell growth and cytotoxicity were measured using a methylthiazol tetrazolium assay. Pc 4 cellular uptake and intracellular distrubtion were determined. For in vitro Pc 4 photodynamic therapy cells were irradiated at 667nm at a fluence of 2.5 J/cm at 48 h. SCID mice were implanted with CaSki and ME-180 cells both subcutaneously and intracervically. Forty-eight h after Pc 4 photodynamic therapy was administered at 75 and 150 J/cm.
The ICs for Pc 4 and Pc 4 photodynamic therapy for CaSki and ME-180 cells as monolayers were, 7.6μM and 0.016μM and >10μM and 0.026μM; as spheroids, ICs of Pc 4 photodynamic therapy were, 0.26μM and 0.01μM. Pc 4 was taken up within cells and widely distributed in tumors and tissues. Intracervical photodynamic therapy resulted in tumor death, however mice died due to gastrointestinal toxicity. Photodynamic therapy resulted in subcutaneous tumor death and growth delay.
Pc 4 photodynamic therapy caused death within cervical cancer cells and xenografts, supporting development of Pc 4 photodynamic therapy for treatment of cervical cancer. Support: P30-CA47904, CTSI BaCCoR Pilot Program.
宫颈癌是全球女性中第二常见的癌症[1]。光动力疗法已用于治疗宫颈上皮内瘤变，效果良好，但很少有研究使用更新的光疗药物。我们评估了在体外和体内使用Pc 4光动力疗法对人宫颈癌细胞的有效性。
将CaSki和ME-180癌细胞培养成单层细胞和球体。使用甲基噻唑四唑蓝法测量细胞生长和细胞毒性。测定Pc 4的细胞摄取和细胞内分布。对于体外Pc 4光动力疗法，在48小时时以2.5 J/cm的能量密度在667nm波长下照射细胞。将CaSki和ME-180细胞皮下和宫颈内植入SCID小鼠体内。在给予75和150 J/cm的Pc 4光动力疗法48小时后。
单层CaSki和ME-180细胞的Pc 4及Pc 4光动力疗法的半数抑制浓度分别为7.6μM和0.016μM以及>10μM和0.026μM；作为球体，Pc 4光动力疗法的半数抑制浓度分别为0.26μM和0.01μM。Pc 4被细胞摄取并广泛分布于肿瘤和组织中。宫颈内光动力疗法导致肿瘤死亡，但小鼠因胃肠道毒性死亡。光动力疗法导致皮下肿瘤死亡和生长延迟。
Pc 4光动力疗法导致宫颈癌细胞和异种移植瘤死亡，支持开发用于治疗宫颈癌的Pc 4光动力疗法。资助：P30-CA47904，CTSI BaCCoR试点项目。
