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目的:探讨靶向融合肽﹛转录反式激活因子(trans-activator of transcription,TAT)-卵巢癌特异性结合肽(ovarian cancer specii c binding peptide,OSBP)-丝裂原活化蛋白激酶激酶6突变体(E)[mitogen-activated protein kinase kinase 6 mutant(E),MKK6(E)]﹜对卵巢癌裸鼠移植瘤的抑制作用及其可能的机制。方法:建立卵巢癌HO8910细胞的裸鼠皮下移植瘤模型,分为实验组[给予TAT-OSBP-MKK6(E)腹腔注射]、阴性对照组(给予TAT-OSBP腹腔注射)和空白对照组(给予0.9%Na Cl溶液腹腔注射),比较3组裸鼠移植瘤的生长速度、体积和裸鼠体质量;TUNEL法、免疫组织化学法和蛋白质印迹法分别检测移植瘤组织中细胞的凋亡情况、增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)的表达以及p38蛋白的表达。结果:实验组裸鼠移植瘤的生长速度滞后于阴性对照组和空白对照组(P<0.05),实验组裸鼠移植瘤体积和裸鼠体质量小于阴性对照组和空白对照组(P均<0.05);而阴性对照组与空白对照组之间的差异无统计学意义(P>0.05)。实验组肿瘤细胞的凋亡指数(apoptosis index,AI)高于阴性对照组和空白对照组(P<0.05),实验组肿瘤组织中PCNA的阳性表达率低于阴性对照组和空白对照组,而p38蛋白的表达水平则相反(P均<0.05);阴性对照组与空白对照组的AI、PCNA阳性表达率及p38蛋白的表达水平之间的差异均无统计学意义(P均>0.05)。结论:靶向融合肽TAT-OSBP-MKK6(E)可抑制卵巢癌裸鼠移植瘤的生长和PCNA的表达,其机制可能与促进细胞凋亡有关。
OBJECTIVE: To investigate the effect of targeted fusion peptide {trans-activator of transcription (TAT) - ovarian cancer specii c binding peptide (OSBP) - mitogen activated protein kinase kinase 6 mutant (E) [mitogen-activated protein kinase kinase 6 mutant (E), MKK6 (E)]} on ovarian cancer xenografts in nude mice and its possible mechanism. Methods: The ovarian cancer HO8910 cells were transplanted subcutaneously in nude mice and divided into experimental group [intraperitoneal injection of TAT-OSBP-MKK6 (E)], negative control group (intraperitoneal injection of TAT-OSBP) and blank control group 0.9% NaCl solution was injected intraperitoneally). The growth rate, volume and nude mice body weight were compared between the three groups. TUNEL, immunohistochemistry and Western blotting were used to detect the apoptosis of the transplanted tumor tissue, Expression of proliferating cell nuclear antigen (PCNA) and p38 protein. Results: The growth rate of nude mice in experimental group lagged behind that in negative control group and blank control group (P <0.05). The volume of tumor xenograft in nude mice and the weight of nude mice in experimental group were lower than those in negative control group and blank control group (P < 0.05). There was no significant difference between the negative control group and the blank control group (P> 0.05). The apoptosis index (AI) in experimental group was higher than that in negative control group and blank control group (P <0.05). The positive expression rate of PCNA in experimental group was lower than that in negative control group and blank control group (P <0.05). There was no significant difference in the positive expression rate of AI and PCNA between the negative control group and blank control group and the expression of p38 protein (all P> 0.05). CONCLUSION: Targeted fusion peptide TAT-OSBP-MKK6 (E) can inhibit the growth of ovarian cancer xenografts in nude mice and the expression of PCNA, which may be related to the promotion of apoptosis.