HIF-1α对乳腺癌细胞增殖及血管生成影响的探讨

Influence of HIF-1α in cell proliferation and angiogenesis of breast cancer

目的:通过检测乳腺组织缺氧诱导因子-1α(hypoxia-inducible factor,HIF-1α)、Ki-67和血管内皮生长因子(vas-cular endothelial growth factor,VEGF)的表达情况,探讨HIF-1α对乳腺癌细胞增殖及血管生成的作用机制。方法:采用免疫组化法检测70例乳腺癌组织及其癌旁组织和10例正常乳腺组织中HIF-1α、Ki-67和VEGF的表达情况。结果:HIF-1α在乳腺癌组织中阳性表达率为78.6%(55/70),在癌旁组织中为45.7%(32/70);Ki-67在乳腺癌组织中阳性表达率为88.6%(62/70),在癌旁组织中为11.4%(8/70);VEGF在乳腺癌组织中阳性表达率为65.7%(46/70),在癌旁组织中为34.3%(24/70)。HIF-1α、Ki-67和VEGF在乳腺正常组织中均未见表达,结果表明,三者在癌组织中的表达显著高于癌旁及正常组织,差异均有统计学意义,P值均<0.01;且与临床分期和淋巴结转移情况密切相关,P<0.05。HIF-1α与Ki-67、VEGF在乳腺癌组织中的表达呈中高度相关,关联系数分别为0.65和0.48;且随着HIF-1α表达增强,Ki-67和VEGF的表达也有增强趋势,P<0.01。结论:乳腺癌组织中HIF-1α、Ki-67和VEGF高表达,与组织恶性程度相关,提示HIF-1α、Ki-67和VEGF可能成为预测乳腺癌发生发展、侵袭转移和预后的重要指标;缺氧可能通过某些机制影响乳腺癌细胞增殖及血管生成,HIF-1α可望成为乳腺癌治疗的一个新靶点,值得进一步研究。

OBJECTIVE： To examine the expression of hypoxia inducible factor-1α （hypoxia-inducible factor 1α, HIF-1α）, tumor cell proliferation antigen Ki-67 and vascular endothelial growth factor （vascular endothelial growth factor, VEGF） in tissue of breast, and investigate the influence of HIF-1α impact on both tumor cell proliferation and angiogenesis in breast cancer tissues. METHODS： Using Immunohistochemistry HRP method to detect expression of HIF-1α, Ki-67 and VEGF in 70 cases of breast cancer and their adjacent tissues as well as 10 cases of normal breast tissue. RESULTS： The expression rates of HIF-1α were 78.6 % （55/70） in breast cancer tissues,and 45.7% （32/70） in adjacent tissues. The positive expression rates of Ki-67 for the two tissues were 88.6% （62/70） and 11.4 % （8/70）. In addition, the positive ex- pression rates of VEGF for the two tissues were 65.7% （46/70） and 34.3% （24/70）. These three factors showed no ex- pression in normal breast tissues. These survey results indicated that expression of the three indicators in breast cancer were significantly higher than that in adjacent tissues and normal tissues（P〈0.01）, and they were closely related with clinical stage and lymph node metastasis（P〈0.05）. The expression intensity of HIF-1α was positively correlated with Ki-67 and VEGF in breast cancer（r values were 0. 65 and 0. 48,and all P〈0.01）. CONCLUSIONS： The expression of HIF-1α,Ki-67 and VEGF are high in breast cancer,which are associated with the malignancy degree of tissue. They may be important indicators of predicting the invasion,metastasis and prognosis in breast cancer. It suggests that H IF-ltx may affect the tumor cell proliferation and angiogenesis through some interaction in breast cancer. It is expected to become a new target for treatment of breast cancer and it is worthy for further study.