照射后NK-92细胞对人卵巢癌细胞杀伤活性的研究

目的研究放射线照射后NK92细胞对人卵巢癌细胞杀伤活性及其成瘤性的影响。方法应用医用电子直线加速器对NK92细胞进行照射处理(800cGy),以体外培养的人卵巢癌细胞株HO8910为靶细胞,以细胞株K562作为对照,应用4h51Cr释放法检测不同效靶比情况下体外培养NK92细胞的杀伤活性。建立人卵巢癌SCID鼠肿瘤模型,观察输注经照射后的NK92细胞对荷瘤鼠的治疗效果。结果(1)体外实验NK92细胞未照射组,效靶比较低时(11、51)对HO8910细胞的杀伤率为39%～45%,随效靶比升高,杀伤率上升,101时杀伤率升为59%,201时杀伤率仅上升了6%;对于K562细胞,杀伤率在58%～71%之间。照射后2d,800cGy组NK92细胞对HO8910细胞不同效靶比的杀伤率比0cGy组略有降低,总体杀伤率在33%～58%之间;对于K562细胞,杀伤率在39%～49%之间。照射后NK92细胞数量进行性下降,第5天细胞死亡;(2)动物实验分别在接种后30、40、50d观察治疗组与对照组肿瘤体积,结果显示,分别减小了78%、56%、20%(P<0.01)。结论NK92细胞对人卵巢癌细胞具有较高的杀伤活性,经放射线照射后仍保留一定的杀伤活性,作为一种生物治疗手段治疗卵巢癌行之有效。

Study on the cytotoxic activity of irradiated NK-92 cells against human ovarian carcinoma

Objective:To study the cytotoxic activity of NK 92 cells against human ovarian cancer cells in vitro and in vivo and the effect of irradiation on NK 92 cytotoxicity.Methods:NK 92 cells were mixed with 51 Cr labeled HO 8910 and K562 cells at different effector to target ratios for a 4h 51 Cr release assay.On the other hand, NK 92 cells were irradiated at 0 and 800 cGy and tested after 2 days for cytotoxicity against HO 8910 cells.In animal experiments, human ovarian carcinoma in a SCID mouse model was devised, and the potential of irradiated NK 92 as immunotherapy for ovarian carcinoma was evaluated.Results:In vitro,unirradiated NK 92 cells displayed high cytotoxicity against HO 8910 with a mean specific lysis of 59% and 65% at 10:1 and 20:1 E:T ratios, while these levels at 1:1(39%) and 5:1(45%) E:T ratios were lower.The cytotoxicity of NK 92 against K562 ranged from 58% to 71%. NK 92 cells maintained up to 33%～58% cytotoxicity against HO 8910 when irradiated with 800cGy after 2 days. In vivo treatment of mouse with irradiated NK 92 cells, tumor size was reduced 78% as compared with control on day 30 after injection and 56% on day 40 and 20% on day 50(P<0.01).Conclusion:NK 92 cells are highly cytotoxic to human ovarian carcinoma both in vitro and in vivo in a mouse model.Irradiated NK 92 cells may be a potentially effective immunotherapeutic modality in human ovarian carcinoma.