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二氢卟吩e6介导的光动力疗法对人子宫内膜腺癌细胞系HEC-1-A的抗癌作用

The Anticancer Effects of Radachlorin-mediated Photodynamic Therapy in the Human Endometrial Adenocarcinoma Cell Line HEC-1-A.

作者信息

Kim Su-Mi, Rhee Yun-Hee, Kim Jong-Soo

机构信息

Department of Obstetrics and Gynecology, College of Medicine, Dankook University, Cheonan, Republic of Korea.

Beckman Laser Institute Korea, Dankook University, Cheonan, Republic of Korea.

出版信息

Anticancer Res. 2017 Nov;37(11):6251-6258. doi: 10.21873/anticanres.12076.

Abstract

AIM

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.

MATERIALS AND METHODS

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.

RESULTS

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.

CONCLUSION

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.

摘要

目的

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。

材料与方法

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。

结果

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。

结论

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。

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