Cao Di, Chu Wai Kit, Ng Tsz Kin, Yip Yolanda W Y, Young Alvin L, Pang Chi Pui, Jhanji Vishal
Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong Eye Hospital, Kowloon, Hong Kong.
Department of Ophthalmology, Prince of Wales Hospital, Shatin, Hong Kong.
Cornea. 2018 Jun;37(6):760-766. doi: 10.1097/ICO.0000000000001569.
Nutlin is a drug that has been reported to activate p53 in various cell lines. We aim to study the effects of Nutlin in pterygium and compare the effects of Nutlin and mitomycin C (MMC) in pterygium cell lines.
Pterygium samples (n = 3) were collected during surgical excision. Normal conjunctival tissues (n = 3) were collected from another quadrant of the same eye. Cell lines were established, and cells from passages 2 to 5 were used. Pterygium and conjunctival cells were treated with different doses of Nutlin and MMC. Cell proliferation and cell migration were measured.
Cell proliferation was reduced by 39-fold after treatment with 50 μM Nutlin. Cell migration was inhibited with increasing dosages of Nutlin (95% and 28% after treating with 2 and 50 μM Nutlin, respectively). Compared with MMC, Nutlin induced more pterygium cell death and less conjunctival cell death at low doses. At 50% lethal dose for pterygium cells, 95% of conjunctival cells survived after Nutlin treatment, whereas only 63% of conjunctival cells survived after MMC treatment. p21 expression was not detectable in MMC-treated pterygium cells but was detectable after Nutlin treatment.
In our study, MMC induced cell death in pterygium and conjunctival cell lines, whereas Nutlin had a targeted impact on pterygium cells. Our results implied that MMC inhibited both pterygium cell proliferation and migration through an apoptosis-independent pathway.
Nutlin是一种据报道可在多种细胞系中激活p53的药物。我们旨在研究Nutlin在翼状胬肉中的作用,并比较Nutlin和丝裂霉素C(MMC)在翼状胬肉细胞系中的作用。
在手术切除过程中收集翼状胬肉样本(n = 3)。从同一只眼睛的另一个象限收集正常结膜组织(n = 3)。建立细胞系,并使用第2至5代的细胞。用不同剂量的Nutlin和MMC处理翼状胬肉和结膜细胞。测量细胞增殖和细胞迁移。
用50μM Nutlin处理后,细胞增殖降低了39倍。随着Nutlin剂量的增加,细胞迁移受到抑制(分别用2μM和50μM Nutlin处理后,细胞迁移抑制率为95%和28%)。与MMC相比,低剂量时Nutlin诱导的翼状胬肉细胞死亡更多,结膜细胞死亡更少。对于翼状胬肉细胞的50%致死剂量,Nutlin处理后95%的结膜细胞存活,而MMC处理后只有63%的结膜细胞存活。在MMC处理的翼状胬肉细胞中未检测到p21表达,但在Nutlin处理后可检测到。
在我们的研究中,MMC在翼状胬肉和结膜细胞系中诱导细胞死亡,而Nutlin对翼状胬肉细胞有靶向作用。我们的结果表明,MMC通过非凋亡途径抑制翼状胬肉细胞增殖和迁移。