Kim Su-Mi, Rhee Yun-Hee, Kim Jong-Soo
Department of Obstetrics and Gynecology, College of Medicine, Dankook University, Cheonan, Republic of Korea.
Beckman Laser Institute Korea, Dankook University, Cheonan, Republic of Korea.
Anticancer Res. 2017 Nov;37(11):6251-6258. doi: 10.21873/anticanres.12076.
We investigated the effect of photodynamic therapy (PDT) using radachlorin on invasion, vascular formation and apoptosis by targeting epidermal growth factor receptor (EGFR)/vascular endothelial growth factor receptor 2 (VEGFR2) signaling pathways in the HEC-1-A endometrial adenocarcinoma cell line.
To investigate the apoptotic pathway, we performed the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay, and western blot analysis. We also evaluated the effects of PDT on tubular capillary formation in and invasion by HEC-1-A cells with a tube formation assay, invasion assay, prostaglandin E2 (PGE2) assay, and western blot analysis.
PDT had anticancer effects on HEC-1-A through activation of the intrinsic pathway of apoptosis via caspase-9 and poly-(ADP-ribose) polymerase (PARP). PDT also inhibited tubular capillary formation in and invasion by HEC-1-A under VEGF pretreatment, that resulted from down-regulation of VEGFR2, EGFR, Ras homolog gene family/ member A (RhoA) and PGE2. These results are indicative of the specificity of radachlorin-mediated PDT to VEGF.
The major advantage of radachlorin-mediated PDT is its selectivity for cancer tissue while maintaining adjacent normal endometrial tissue. Therefore, radachlorin-mediated PDT might offer high anticancer efficacy for endometrial adenocarcinoma and an especially useful modality for preserving fertility.
我们研究了使用拉达氯林的光动力疗法(PDT)通过靶向人子宫内膜腺癌HEC-1-A细胞系中的表皮生长因子受体(EGFR)/血管内皮生长因子受体2(VEGFR2)信号通路对侵袭、血管形成和细胞凋亡的影响。
为了研究细胞凋亡途径,我们进行了3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)试验、末端脱氧核苷酸转移酶dUTP缺口末端标记(TUNEL)试验和蛋白质免疫印迹分析。我们还通过管腔形成试验、侵袭试验、前列腺素E2(PGE2)试验和蛋白质免疫印迹分析评估了PDT对HEC-1-A细胞的管状毛细血管形成和侵袭的影响。
PDT通过激活caspase-9和聚(ADP-核糖)聚合酶(PARP)介导的细胞凋亡内源性途径对HEC-1-A具有抗癌作用。在VEGF预处理下,PDT还抑制了HEC-1-A的管状毛细血管形成和侵袭,这是由于VEGFR2、EGFR、Ras同源基因家族成员A(RhoA)和PGE2的下调所致。这些结果表明拉达氯林介导的PDT对VEGF具有特异性。
拉达氯林介导的PDT的主要优点是其对癌组织具有选择性,同时保留相邻的正常子宫内膜组织。因此,拉达氯林介导的PDT可能为子宫内膜腺癌提供高抗癌疗效,并且是一种特别有用的保留生育能力的治疗方式。