摘要
目的:探讨干扰素α-2b及联合化疗药物顺铂对人雄激素非依赖性前列腺癌裸鼠皮下移植瘤生长的影响及可能的作用机制。方法:将人雄激素非依赖性前列腺癌细胞株PC-3接种于20只裸鼠右背部皮下建立荷瘤裸鼠模型。然后随机分四组,每组5只。对照组(A组)注射生理盐水;干扰素组(B组)每天皮下注射干扰素α-2b(10 000 IU/d);顺铂组(C组)腹腔注射2次/周,每次每只1.5 mg/kg;干扰素加顺铂组(D组):每天皮下注射干扰素α-2b(10 000 IU/d),顺铂2次/周腹腔注射,每次每只1.5 mg/kg。用药4周后处死裸鼠,检测肿瘤的体积,瘤重,去瘤鼠重,观察治疗效果及副作用。应用免疫组化方法检测治疗后各组肿瘤组织中环氧合酶-2(COX-2)和血管内皮生长因子(VEGF)的蛋白表达;CD34标记血管内皮细胞测定肿瘤的为血管密度(MVD);应用TUNEL方法检测肿瘤细胞的凋亡。结果:①各治疗组肿瘤的生长较对照组均有不同程度的抑制;联合用药组与其他三组相比,抑制效果最为显著,差异有统计学意义(P<0.01);治疗后各组去瘤裸鼠体重相互比较,差异均无统计学意义(P>0.05);②各组肿瘤组织中COX-2和VEGF均有不同程度的表达,其中联合用药组和干扰素α-2b组肿瘤组织中的COX-2和VEGF的表达水平显著低于对照组,差异有统计学意义(P<0.05),MVD减少及肿瘤组织中凋亡细胞的比例增加,与对照组比较,差异有统计学意义(P<0.05)。结论:干扰素α-2b联和顺铂均可抑制荷瘤裸鼠雄激素非依赖前列腺癌的生长,诱导肿瘤细胞的凋亡。干扰素α-2b抗肿瘤血管的生成是其抑制肿瘤生长的机制之一;干扰素α-2b与顺铂合用可达到较好的协同作用,抑瘤效更加明显,可能应用于前列腺肿瘤的联合化疗。
Objective To investigate the effects and mechanism of interferon alpha-2b（IFNα-2b） combined with cisplation for the growth of hormone-refractary prostatic carcinoma implants in nude mice.Method Nude mice bearing human hormone-refractory prostatic carcinoma（HRPC） were randomized into the following groups 10 days after implantation of human prostate carcinoma cell PC-3：group A,saline,sc,qd（control）;group B,IFNα-2b 10 000 IU/d,sc,qd;group C,criplation 1.5 mg/kg,ip,biw and group D,IFNα-2b 10 000 IU/d,sc,qd plus cisplation 1.5 mg/kg,ip,biw,respectively;Total mice were sacrificed four weeks after administration.Then the volume and weight of tumor,the post-therapeutic weight of mice were studied after 28 consecutive days.The COX-2 and VEGF expression of tumors were detected by immunohistochemistry.Microvessel density（MVD） was counted by endothelial cells immunostained by anti-CD34 antibody.The TUNEL assay was used to examine the apoptosis alteration of tumor cell in nude mice after treatment with saline,IFNα-2b,cisplatin and combination group.Results The tumor growth of every therapeutic groups were significantly different from the controls.IFNα-2b combined with cisplation group had the most inhibitory effect of the growth of tumor than the others（P0.01）.The weight changes of the mice between every post-therapeutic group did not have difference（P0.05）.Compared with the control and cisplation group,the protein of COX-2 and VEGF expressed more lower than in IFNα-2b-treament and combination group tumor cells（P0.05）.The amount of MVD in the IFNα-2b-treated and combination group tumor tissues was significantly lower than in control and cisplation group.Conclusion INFα-2b and cisplation can inhibit the growth of prostate cancer.The mechanism of the inhibition of the implanted tumor growth and induction cell apoptosis with IFNα-2b treatment may be associated with down-regulation of COX-2 and VEGF expression;INFα-2b inhibits the tumor angiogenesis,combining with chemical drug may have syn
出处
《吉林医学》
CAS
2011年第10期1879-1881,共3页
Jilin Medical Journal
关键词
前列腺癌
干扰素Α-2B
COX-2
VEGF
MVD
Prostate cancer
Interferon α-2b
Cyclooxygenase-2
Vacular endothelial growth factor
Microvessel density
