Enhanced antitumor efficacy of a novel oncolytic adenovirus combined with temozolomide in the treatment of melanoma in vivo
Enhanced antitumor efficacy of a novel oncolytic adenovirus combined with temozolomide in the treatment of melanoma in vivo
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新型溶瘤腺病毒联合替莫唑胺增强体内治疗黑色素瘤的抗肿瘤功效
DOI：
10.1007/s00432-014-1763-7
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发表时间：
2015-01-01
影响因子：
3.6
通讯作者：
Liu, Yan-Qun
中科院分区：
文献类型：
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作者：
Jiang, Guan;Sun, Chao;Liu, Yan-Qun
本研究旨在探讨Ki 67-ZD 55-IL-24联合替莫唑胺（TMZ）对小鼠黑色素瘤的治疗作用。（2 x 10（6））随机分配至右侧腹接受磷酸盐缓冲盐水（PBS）、Ki 67-ZD 55、Ki 67-ZD 55-IL-24、TMZ、TMZ + Ki 67-ZD 55、和TMZ + Ki 67-ZD 55-IL-24。干预后10 d每组处死6只小鼠，检测IL-24 mRNA和蛋白表达。监测剩余小鼠的体重变化曲线和肿瘤生长曲线，并于干预后30 d处死。切除肿瘤并称重。HE染色观察肿瘤组织形态，TUNEL法检测凋亡指数，AnnexinV-FITC/PI双染色检测凋亡细胞率。Ki 67-ZD 55-IL-24组与TMZ + Ki 67-ZD 55-IL-24组之间IL-24表达无显著差异。免疫组化和Western blot结果显示，Ki 67-ZD 55和Ki 67-ZD 55-IL-24均能显著降低MGMT的表达。毒性评估表明，接受TMZ的三组小鼠在治疗后表现出显著的体重减轻。HE染色显示TMZ + Ki 67-ZD 55-IL-24组肿瘤细胞核分裂明显减少。TMZ + Ki 67-ZD 55-IL-24组肿瘤组织的凋亡指数和凋亡细胞率均显著高于其他各组（P均< 0.05），提示TMZ + Ki 67-ZD 55-IL-24治疗恶性黑色素瘤具有良好的应用前景。
The aim of this study was to investigate the effect of Ki67-ZD55-IL-24 with temozolomide (TMZ) against melanoma in mice.Seventy-eight mice with subcutaneous injection of A375 cells (2 x 10(6)) into the right flank were randomized to receive phosphate buffered saline (PBS), Ki67-ZD55, Ki67-ZD55-IL-24, TMZ, TMZ + Ki67-ZD55, and TMZ + Ki67-ZD55-IL-24. Six mice were killed in each group 10 days after intervention for detecting IL-24 mRNA and protein expression. The remaining mice were monitored to draw the body weight change curve and tumor growth curve, and killed 30 days after intervention. Tumors were excised and weighted. The morphology of tumor tissues was determined by hematoxylin and eosin (HE) staining, and the apoptosis index and rate of apoptotic cells were determined by TUNEL assay and AnnexinV-FITC/PI double staining, respectively.The Ki67-ZD55-IL-24-treated group generated much more reactive oxygen species than the untreated group. There was no significant difference in IL-24 expression between Ki67-ZD55-IL-24 and TMZ + Ki67-ZD55-IL-24 groups. Immunohistochemical analysis and Western blot revealed that both the Ki67-ZD55 and Ki67-ZD55-IL-24 could significantly reduce the expression of MGMT. Toxicity assessments demonstrated that mice in the three groups that received TMZ exhibited significant body weight loss following treatment. HE staining showed that TMZ + Ki67-ZD55-IL-24 group had much fewer karyokinesis in the tumors, compared with other groups. The apoptosis index of tumor tissues and the rate of apoptotic cells were significantly higher in TMZ + Ki67-ZD55-IL-24 group than in other groups (all P < 0.05).These findings indicate this novel strategy holds promising potentials for treatment of malignant melanoma.