靶向Survivin的shRNA对皮肤鳞状细胞癌生长抑制作用的实验研究

Human skin squamous cell carcinoma (SCC) is one of the most common dermatological malignancies for which the current treatment is rather limited and accompanied with some undesired side effects. Therefore the genetic biological therapy of high efficiency and low toxicity naturally becomes a hot research topic for cancer prevention and treatment. Based on the current research results, survivin is the most potent inhibitor of apoptosis found so far. Due to its specific expression and dual effect of tumor cell proliferation and apoptosis suppression, survivin has been percieved as an ideal target for tumor genetic therapy research. The objective of this study is to clarify the therapeutic efficacy of shRNA-mediated survivin knock-down by using the designed survivin- shRNA to the SCC xenograft model in nude mice with the cultured human SCC A431 cells lines. The inhibitory effect and the toxic side effects were detected by observing of tumor growth. Moreover the molecular inhibition mechanism of SCC was investigated by detectiing the expression survivin and the relative downstream apoptotic factors such as caspase-3, caspase-7, caspase-8 and caspase-9, which would provide a theoretical basis for the clinical treatment to SCC by survivin-shRNA. Therefore this project has the important theoretical and practical clinical values.

皮肤鳞状细胞癌（SCC）为皮肤科常见恶性肿瘤，目前治疗方法有限且毒副作用大，因此，高效低毒的基因生物疗法成为癌症预防和治疗领域的一个研究热点。Survivin是迄今为止发现的作用最强的凋亡抑制因子。由于Survivin表达的特异性及对肿瘤细胞促增殖和抑凋亡的双重作用，使其成为肿瘤基因治疗研究一个理想靶目标。为明确Survivin-shRNA技术能否作为治疗SCC的有效方法，本实验拟通过培养人SCC A431细胞株，建立裸鼠SCC移植瘤模型，设计合成Survivin-shRNA，分组进行干预，观察shRNA对SCC细胞株及移植瘤生长的抑制效果，了解其毒副作用，检测Survivin及其下游凋亡执行因子caspase-3、7 、8、9的表达，探讨其对SCC抑制作用的分子机制，为Survivin-shRNA用于临床治疗SCC提供理论基础。本研究对治疗SCC，具有重要的理论意义和实际临床应用价值。

皮肤鳞状细胞癌（SCC）为皮肤科常见恶性肿瘤，目前治疗方法有限且毒副作用大，因此，高效低毒的基因生物疗法成为癌症预防和治疗领域的一个研究热点。本实验通过培养人SCC A431细胞株，建立裸鼠SCC移植瘤模型，设计合成Survivin-shRNA，分组进行干预，观察shRNA对SCC细胞株及移植瘤生长的抑制效果，了解其毒副作用，检测Survivin及其下游凋亡执行因子caspase-3、7 、8、9的表达。通过本课题实验结果初步得出结论：靶向Survivin-shRNA对SCC抑制作用是通过促进肿瘤细胞凋亡，抑制肿瘤细胞分裂增殖等实现的，其机制可能与靶向Survivin-shRNA可降低SVV的表达，使Caspase8、9活化，后者激活Caspase3，使其蛋白表达增高，从而促使细胞凋亡，而形成的凋亡蛋白又激活P53，从而进一步扩大凋亡效应有关。本实验明确Survivin-shRNA对SCC抑制作用的分子机制，为Survivin-shRNA用于临床治疗SCC提供理论基础。本研究对治疗SCC，具有重要的理论意义和实际临床应用价值。