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目的探讨乙酰肝素酶反义寡核苷酸(ASODN)对人恶性黑素瘤裸鼠皮下移植瘤的抑制作用。方法分空白组、无关序列(N-ODN)组、10μmol/LASODN组、20μmol/LASODN组和30μmol/LASODN组5组,以脂质体包埋分别转染人恶性黑素瘤细胞株A375,后接种于裸鼠皮下,观察裸鼠移植瘤体积变化,并采用原位杂交、免疫组化法检测移植瘤中乙酰肝素酶mRNA及其蛋白表达的变化。结果接种6周后,各ASODN组的裸鼠移植瘤体积均显著小于N-ODN组和对照组(P均<0.05);各ASODN组裸鼠移植瘤中乙酰肝素酶mRNA和蛋白水平均较对照组、N-ODN组显著下调(P均=0.000)。结论乙酰肝素酶ASODN对人恶性黑素瘤裸鼠皮下移植瘤具有抑制作用。
Objective To investigate the inhibitory effect of heparanase antisense oligonucleotide (ASODN) on subcutaneous xenografts of human malignant melanoma in nude mice. Methods N-ODN group, 10μmol / L ASODN group, 20μmol / L ASODN group and 30μmol / L ASODN group were divided into 5 groups and were transfected into human melanoma cell line A375 by liposome respectively The mice were inoculated subcutaneously into nude mice to observe the volume changes of transplanted tumor in nude mice. The changes of heparanase mRNA and protein expression in the transplanted tumor were detected by in situ hybridization and immunohistochemistry. Results After 6 weeks of inoculation, the xenograft tumor volume in nude mice in ASODN group was significantly smaller than that in N-ODN group and control group (all P <0.05). The mRNA and protein levels of heparanase in nude mice xenografted with ASODN In the control group, the N-ODN group was significantly down-regulated (P = 0.000). Conclusion Heparanase ASODN can inhibit the growth of human malignant melanoma subcutaneously in nude mice.