Sun Quanhong, Sakaida Tsukasa, Yue Wen, Gollin Susanne M, Yu Jian
University of Pittsburgh Cancer Institute, Hillman Cancer Center Research Pavilion, Suite 2.26H, 5117 Centre Avenue, Pittsburgh, PA 15213, USA.
Mol Cancer Ther. 2007 Dec;6(12 Pt 1):3180-8. doi: 10.1158/1535-7163.MCT-07-0265.
Head and neck squamous cell carcinoma (HNSCC) ranks the eighth most common cancer worldwide. The patients often present with advanced disease, which responds poorly to chemoradiation therapy. PUMA is a BH3-only Bcl-2 family protein and a p53 target that is required for apoptosis induced by p53 and various chemotherapeutic agents. In this study, we found that PUMA induction by chemotherapeutic agents is abrogated in most HNSCC cell lines. Adenoviral gene delivery of PUMA induced apoptosis and chemosensitization more potently than did adenoviral delivery of p53 in HNSCC cells. Finally, we showed that PUMA suppressed the growth of HNSCC xenograft tumors and sensitized them to cisplatin through induction of apoptosis. Our data suggest that absence of PUMA activation in HNSCC cells contributes to chemoresistance and that gene therapy with PUMA might be an efficient substitute for p53 to enhance the responses of HNSCC cells to chemotherapy.
头颈部鳞状细胞癌（HNSCC）是全球第八大常见癌症。患者常表现为晚期疾病，对放化疗反应不佳。PUMA是一种仅含BH3结构域的Bcl-2家族蛋白，是p53的靶标，p53和各种化疗药物诱导的细胞凋亡都需要它。在本研究中，我们发现大多数HNSCC细胞系中化疗药物诱导的PUMA表达被消除。在HNSCC细胞中，腺病毒介导的PUMA基因传递比腺病毒介导的p53传递更有效地诱导细胞凋亡和化学增敏。最后，我们表明PUMA抑制HNSCC异种移植肿瘤的生长，并通过诱导细胞凋亡使其对顺铂敏感。我们的数据表明，HNSCC细胞中PUMA激活的缺失导致化疗耐药，PUMA基因治疗可能是增强HNSCC细胞对化疗反应的p53的有效替代方法。
