Combination of PTEN gene therapy and radiation inhibits the growth of human prostate cancer Xenografts
Combination of PTEN gene therapy and radiation inhibits the growth of human prostate cancer Xenografts
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DOI：
10.1089/hum.2006.17.975
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发表时间：
2006-10-01
影响因子：
4.2
通讯作者：
Rosser, Charles J.
中科院分区：
文献类型：
--
作者：
Anai, Satoshi;Goodison, Steve;Rosser, Charles J.
前列腺癌对放射治疗的抵抗与Bcl-2过度表达异常有关，Bcl-2是一种与细胞凋亡抑制相关的癌基因。在这项研究中，我们评估了磷酸酶和紧张素同源物（PTEN）的过表达（一种已知抑制Bcl-2表达的蛋白质）与放射治疗的结合是否会抑制接种到胸腺小鼠皮下的表达Bcl-2的人前列腺癌细胞的增殖。与单独治疗相比，腺病毒载体表达的PTEN （AdPTEN）和辐射（5 Gy）联合治疗可显著抑制异种移植物肿瘤的生长。第48天，未治疗对照组的中位肿瘤大小为1030 mm(3)，单独放疗组为656 mm(3)，单独AdPTEN组为640 mm(3)，联合治疗组为253 mm(3) （p < 0.001）。所有病例的治疗耐受性良好。联合治疗还能增强细胞凋亡（p = 0.048），抑制细胞增殖（p = 0.005），抑制肿瘤诱导的新生血管（p = 0.030）。有趣的是，这种治疗不仅增加了肿瘤细胞的凋亡，也增加了肿瘤相关内皮细胞的凋亡。总之，这些发现表明，AdPTEN强烈抑制人类前列腺肿瘤的生长，特别是当与放射治疗联合使用时，这种作用是通过诱导细胞凋亡、抑制血管生成和细胞增殖介导的。
The resistance of prostate cancers to radiation therapy has been linked to abnormalities in overexpression of Bcl-2, an oncogene associated with inhibition of apoptosis. In this study, we evaluated whether the combination of the overexpression of phosphatase and tensin homolog (PTEN), a protein known to inhibit Bcl-2 expression, and radiation therapy would inhibit proliferation of Bcl-2-expressing human prostate cancer cells inoculated into the subcutis of athymic mice. Compared with either treatment alone, the combination of adenoviral vector-expressed PTEN (AdPTEN) and radiation (5 Gy) significantly inhibited xenograft tumor growth. Median tumor size on day 48 was 1030 mm(3) in untreated controls, 656 mm(3) in mice treated with radiation (5 Gy) alone, 640 mm(3) in mice treated with AdPTEN alone, and 253 mm(3) in mice treated with the combination (p < 0.001). Treatment was well tolerated in all cases. Combination treatment also enhanced apoptosis (p = 0.048), inhibited cellular proliferation (p = 0.005), and inhibited tumor-induced neovascularity (p = 0.030). Interestingly, this treatment increased apoptosis not only in tumor cells but also in tumor-associated endothelial cells. Together, these findings indicate that AdPTEN strongly inhibits the growth of human prostate tumors, especially when combined with radiation therapy, and that this effect is mediated by the induction of apoptosis and by the inhibition of angiogenesis and cellular proliferation.