胃癌是我国最常见的恶性肿瘤之一，且易对传统化疗药物产生耐药，寻找低毒、高效、天然的药物治疗胃癌意义重大。申请者前期研究发现在胃癌细胞和胃癌裸鼠皮下移植瘤模型中天然植物单体百里醌可抑制肿瘤细胞增殖、诱导其凋亡，且呈时间和浓度依赖，并可能与PTEN、STAT3信号通路相关。本项目在前期研究基础上拟建立胃癌耐药细胞株和胃癌裸鼠原位移植瘤模型，分别应用慢病毒介导的PTEN基因沉默和过表达技术、STAT3特异性抑制剂阻断技术，检测胃癌细胞（包括胃癌耐药细胞）及胃癌裸鼠原位移植瘤模型中PTEN和STAT3相关信号通路基因及蛋白活性变化，以验证PTEN、STAT3信号通路在百里醌抑制胃癌细胞（包括胃癌耐药细胞）增殖、诱导凋亡中发挥作用，并探讨两条信号通路之间的相互关系，从而揭示百里醌在胃癌细胞（包括胃癌耐药细胞）中抑制增殖、诱导凋亡的具体作用机制，为临床应用百里醌治疗胃癌提供理论依据。

Gastric cancer is one of the most common malignant tumor, and easily to resist to traditional chemotherapy drugs, so to explore low toxicity, high effective natural compound is of great importance. Initial studies found in gastric tumor cells and nude mouse mice subskin transplanted model, the natural plant monomer thymoquinone (TQ) can inhibit proliferation and induce apoptosis in gastric cancer, which were in dose- and time-dependent manner, and may be related with PTEN and STAT3 signal pathway. Our research plans to, on the base of previous studies, establish the gastric cancerous drug-resistant cells and orthotopic transplantation tumor mice. One way is to use lentivirus-mediated gene silencing and overexpression of PTEN, and the other is to use specific inhibitor to interfere STAT3 phosporylation. We will detect mRNAs and proteins of PTEN and STAT3 signal pathways to verify the two signal pathways may play essential roles in the regulation of TQ inhibiting proliferation and inducing apoptosis in tumor cells (including drug-resistant cells) and orthotopic transplantation tumor mice. We will further explore the relationship between them in order to make sure the specific mechanism that through PTEN and STAT3 signaling pathways. TQ can inhibit proliferation and induce apoptosis, in order to provide the theoretical foundation for TQ in the clinic. It suggests that TQ may provide a novel target for treatment of gastric cancer patients.

胃癌是我国常见的恶性肿瘤，且易对传统化疗药物产生耐药，严重危害国人健康。申请者前期研究发现在胃癌细胞和胃癌裸鼠皮下移植瘤模型中天然植物单体百里醌可抑制肿瘤细胞增殖、诱导其凋亡，且呈时间和浓度依赖，并可能与PTEN、STAT3 信号通路相关。本项目在前期研究基础上，分别应用PTEN 基因沉默和过表达技术、STAT3 特异性抑制剂阻断技术，检测胃癌细胞（包括胃癌耐药细胞）及胃癌裸鼠移植瘤模型中PTEN 和STAT3 相关信号通路基因及蛋白活性变化，以验证PTEN、STAT3 信号通路在百里醌抑制胃癌细胞（包括胃癌耐药细胞）增殖、诱导凋亡中发挥作用，并探讨了两条信号通路之间的相互关系。本研究阐明了百里醌在胃癌细胞（包括胃癌耐药细胞）中抑制增殖、诱导凋亡的具体作用机制，为临床应用百里醌治疗胃癌提供理论依据。