汉黄芩素对人卵巢癌细胞株SKOV3裸鼠移植瘤生长及端粒酶活性的抑制作用

目的端粒酶在多种肿瘤细胞中高表达,可能是肿瘤分子靶向治疗的一个理想靶点。已有的研究表明,汉黄芩素体外具有抑制肿瘤细胞端粒酶活性和肿瘤细胞增殖的作用。该研究旨在评价汉黄芩素对人卵巢癌SKOV3细胞裸鼠移植瘤生长及端粒酶活性是否具有抑制作用。方法将移植人卵巢癌SKOV3细胞的裸鼠随机分为5组:汉黄芩素高剂量组(600mg·kg-1)、汉黄芩素低剂量组(300mg·kg-1)、空白对照组、顺铂治疗组(3mg·kg-1)和联合用药(顺铂+汉黄芩素)组,定期检测裸鼠的体重及肿瘤体积,裸鼠移植瘤组织分别提取DNA、RNA和蛋白质,用Southern印迹杂交法测定端粒长度、RT-PCR扩增观察端粒酶基因hTERT的表达、TRAP-PCR-银染法测定端粒酶活性。结果动物实验表明,汉黄芩素对SKOV3移植瘤有明显的抑瘤作用,高剂量组抑瘤率达56.67%(与对照组比较,P=0.002);低剂量组抑瘤率达38.10%(P=0.019),化疗组抑瘤率达50.83%(P=0.004),联合用药(顺铂+汉黄芩素)组的抑瘤率为66.9%,优于单独使用组(P=0.002);不同浓度汉黄芩素组肿瘤组织的端粒长度与空白对照组比较差异无显著性,汉黄芩素对瘤体端粒酶基因hTERT表达、端粒酶活性均有抑制作用,而且作用强度与剂量有关。结论汉黄芩素在体内具有抗肿瘤和抑制端粒酶活性的作用,抑制强度与剂量成正比,抑瘤率与顺铂合用有相加的作用。

The inhibitory role of wogonin on tumor growth and telomerase activity of human ovarian cancer SKOV3 cell line xenograf in nude mice

Aim Telomerase is highly expression in most tumor cells, and it is an ideal target for cancer molecular targeting therapy. It has been proved that wogonin effectively inhibits telomerase activity and tumor cell growth in vitro. The study was to explore the inhibitory effect of wogonin on the growth of tumor and telomerase activity of implanted human ovarian cancer cell line SKOV3 in nude mice. Methods Nude mice with implanted human ovarian cancer cells SKOV3 were randomly divided into five groups, viz. the high dose group of Wogonin(600 mg·kg-1),low dose group of Wogonin(300 mg·kg-1),normal control group, cisplatin therapy group(3 mg·kg-1), and combined therapy group(cisplatin plus wogonin).The weight of nude mice and the volume of tumor were regularly measured. DNA、RNA and protein were extracted from the tumor tissue. The length of telomere was examined by Southern blot. The expression of telomerase hTERT gene was detected by RT-PCR. The telomerase activity was examined by TRAP-PCR-silver staining. Results The wogonin significantly inhibit the growth of tumor when compared with controlled group.The inhibitory rate of high dose group and low dose group were 56.67% (P=0.002) and 38.10%(P=0.019), respectively. The inhibition rate of cisplatin therapy group was 50.83%(P=0.004). The suppress rate of combined group reached 66.9% and higher than any single therapy(P=0.002). The length of telomere in different concentration groups of wogonin was the same as that in the control group.Wogonin inhibited the expression of telomerase gene hTERT and telomerase activity. The inhibition is related to the dose of wogonin. Conclusion Wogonin suppresses the growth and telomerase activity of tumor. The inhibitory effect is related to the dose of wogonin. Combination of wogonin and cisplatin increase the inhibitory rate in nude mice tumor.