Department of Medicine, Pennsylvania State University College of Medicine, Penn State Hershey Cancer Institute, Hershey, PA, USA.
Cancer Biol Ther. 2009 Oct;8(19):1831-7. doi: 10.4161/cbt.8.19.9592.
The prostate apoptosis response protein 4 (Par-4), a tumor suppressor, has been shown to induce apoptosis in cancer cells. While reduced Par-4 expression has been linked to survival of some cancers, its involvement in colon cancer has not been well documented. To explore the feasibility of increasing Par-4 in colon cancer to induce apoptosis, the human colon cancer cell line, HT29, was transfected to overexpress Par-4. In these cells, overexpressed Par-4 led to increased apoptosis in the presence of 5-fluorouracil. Subsequently, PAR-4 cDNA was packaged in nanoliposomal particles. Treating cells with the Par-4 nanoliposomes also increased susceptibility to 5-FU. These nanoliposomes were used to deliver Par-4 plasmid to tumors growing in nude mice from wild type HT29 cells. Results showed that nanoliposomes effectively delivered plasmid DNA to tumors in vivo. Again, tumors in mice treated with the Par-4 nanoliposomes were more susceptible to 5-FU treatment. This suggests that upregulation of Par-4 expression is a potentially useful mechanism to enhance the current chemotherapeutic regimen for colon cancer. Packaging Par-4 cDNA in nanoliposomal particles is a promising delivery method to increase response to chemotherapy.
前列腺凋亡反应蛋白 4（Par-4）是一种肿瘤抑制因子，已被证明可诱导癌细胞凋亡。虽然 Par-4 表达降低与某些癌症的存活有关，但它在结肠癌中的作用尚未得到很好的记录。为了探索在结肠癌中增加 Par-4 以诱导凋亡的可行性，将人结肠癌细胞系 HT29 转染以过表达 Par-4。在这些细胞中，过表达的 Par-4 在存在 5-氟尿嘧啶的情况下导致细胞凋亡增加。随后，将 PAR-4 cDNA 包装在纳米脂质体颗粒中。用 Par-4 纳米脂质体处理细胞也增加了对 5-FU 的敏感性。这些纳米脂质体被用于将 Par-4 质粒递送至从野生型 HT29 细胞生长的裸鼠中的肿瘤。结果表明，纳米脂质体有效地将质粒 DNA递送至体内肿瘤。同样，用 Par-4 纳米脂质体治疗的小鼠中的肿瘤对 5-FU 治疗更敏感。这表明上调 Par-4 表达是增强当前结肠癌化疗方案的一种潜在有用机制。将 Par-4 cDNA 包装在纳米脂质体颗粒中是一种有前途的递药方法，可以增加对化疗的反应。
