血根碱对卵巢癌细胞生长及放射敏感性的影响

Effect of sanguinarine on the growth and radiosensitivity of human ovarian cancer cells

目的探讨血根碱对卵巢癌SK-OV-3细胞的生长及放射敏感性的影响。方法采用MTT法和克隆形成法检测血根碱处理后卵巢癌SK—OV-3细胞的生长；流式细胞仪分析方法观察血根碱对细胞周期分布和细胞凋亡的影响；AnnexinV／PI法观察血根碱联合辐照对细胞凋亡的影响。结果0—5μmol／L血根碱处理24和48h后，细胞生长的抑制与血根碱处理的剂量和时间成正相关（r=0．96和0．97），半数细胞生长抑制的浓度（IC50）分别为3．02和1．11μmol／L。血根碱处理导致了包括细胞变圆、皱缩，漂浮细胞增多等细胞形态学的改变。Sub．G，凋亡峰随血根碱浓度上升而增高，并出现G0／G1期细胞周期阻滞。0．5μmol／L血根碱预处理24h后经6Gy的x射线辐照，早期凋亡细胞从10．28％增加至43．28％（t=19．41，P〈0．01），晚期凋亡细胞从20．26％增加至30．80％（t=8．78，P〈0．01）。采用多靶单击模型拟合曲线发现血根碱＋X射线组与X射线单独照射组的放射增敏比（SERD。）达1．625，即低浓度的血根碱可以增加卵巢癌细胞的放射敏感性。结论血根碱可以显著抑制卵巢癌SK-OV-3细胞的生长，诱导细胞凋亡和周期阻滞，而且在低剂量下，血根碱可以增加卵巢癌细胞的放射治疗敏感性。

Objective To study the effect of sanguinarine on the growth and radiosensitivity of ovarian cancer SK-OV-3 cells. Methods Cell growth was determined by MTT and clonogenic assay. Cell cycle analysis was performed by flow cytometry assay. The cell apoptosis was analyzed by Annexin V/PI assay. Results Sanguinarine inhibited SK-OV-3 cell growth in a dose-and time-dependent fashion and its IC50 values were 3.02 and 1.11 μmol/L at 24 and 48 h, respectively. Sanguinarine also significantly triggered a sub-G1 peak, an indicator of apoptosis, and caused a G0/G1 arrest. Furthermore, the cell apoptosis induced by X-irradiation was significantly increased at 6 Gy when the cells were pre-treated with sanguinarine, in which the early apoptotic population increased from 10.28% to 43.28% （t = 19.41, P 〈 O. 01 ） and the late apoptotic population increased from 20. 26% to 30. 80% （ t = 8.78, P 〈 0.01 ）. The multi-target click model was used to fit survival curves and the SER of sanguinarine treatment approached to 1. 625 at the dose of Do. Conclusions Sanguinarine could inhibit SK-OV-3 cell growth by inducing apoptosis and cell cycle arrest and enhance cell radiosensitivity at low doses.