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目的:探讨γ射线照射后的IL-15基因修饰的NK细胞(简称NK-ustc细胞)对原代卵巢癌细胞的体内外杀伤活性。方法:分离卵巢癌患者腹水原代卵巢癌细胞。不同剂量γ射线(0、1、2、4、8、16 Gy)照射NK-ustc细胞,3H-TdR掺入法检测照射后NK-ustc细胞的增殖情况,51Cr释放法检测NK-ustc细胞对K562和原代卵巢癌细胞的杀伤活性。建立人裸鼠荷卵巢癌模型,随机分为NK-ustc治疗组(模型鼠腹腔注射辐照后的NK-ustc细胞)和培养基对照组,同时设空白对照组(正常裸鼠腹腔注射辐照后的NK-ustc细胞),观察各组裸鼠体重、腹围及生存期。结果:1、2、4、8、16 Gy辐照后NK-ustc细胞的增殖率分别为(62.1±9.8)%、(41.3±8.7)%、(14.6±4.1)%、(0.1±0.03)%和(0.2±0.04)%。当效靶比为10∶1时,0、8 Gy辐照后NK-ustc细胞对K562的杀伤率分别为(45.4±8.9)%和(43.1±6.4)%,对原代卵巢癌细胞的杀伤率分别为(54.6±6.4)%和(48.3±5.8)%,说明辐照不影响NK-ustc细胞的杀伤活性(P>0.05)。辐照后NK-ustc细胞治疗组荷瘤小鼠的中位生存期为75 d,对照组为39 d(P<0.05),空白对照组小鼠全部存活。结论:γ射线照射可有效抑制NK-ustc细胞增殖,但保留该细胞对原代卵巢癌细胞的杀伤活性。
Objective: To investigate the in vivo and in vitro cytotoxic activity of IL-15 gene modified NK cells (NK-ustc cells) on primary ovarian cancer cells after γ-ray irradiation. Methods: Primary ovarian cancer cells were isolated from patients with ovarian cancer. The NK-ustc cells were irradiated with different doses of γ ray (0, 1, 2, 4, 8, 16 Gy), the proliferation of NK-ustc cells was detected by 3H- TdR incorporation method, K562 and primary ovarian cancer cells. The nude mice bearing ovarian cancer model were established and randomly divided into NK-ustc treatment group (intraperitoneal injection of irradiated NK-ustc cells) and culture medium control group, while blank control group (normal nude mice intraperitoneal injection of irradiation After NK-ustc cells), observe the body weight, abdominal circumference and survival of nude mice in each group. RESULTS: The proliferation rates of NK-ustc cells were (62.1 ± 9.8)%, (41.3 ± 8.7)%, (14.6 ± 4.1)%, (0.1 ± 0.03)%, % And (0.2 ± 0.04)%. When the effective target ratio was 10: 1, the killing rates of NK-ustc cells to K562 cells after irradiated with 0,8 Gy were (45.4 ± 8.9)% and (43.1 ± 6.4)%, respectively, killing the primary ovarian cancer cells (54.6 ± 6.4)% and (48.3 ± 5.8)%, respectively, indicating that irradiation did not affect the cytotoxic activity of NK-ustc cells (P> 0.05). After irradiation, the median survival time of tumor-bearing mice was 75 days in NK-ustc cell-treated group, 39 days in control group (P <0.05), and all the mice in blank control group survived. Conclusion: γ-ray irradiation can effectively inhibit the proliferation of NK-ustc cells, but retain the cytotoxic activity of the cells on primary ovarian cancer cells.