天然抗癌活性化合物C18H17NO6抗肺癌作用及促进肺癌细胞凋亡的机制研究

肺癌发病率和致死率位列恶性肿瘤榜首。课题组前期研发的化合物C18H17NO6(简称M）的抗癌活性优于顺铂和紫杉醇，有良好的药物安全性和体外抗癌活性。研究发现M可高效抑制肺癌细胞增殖，诱导G2/M期阻滞，促进细胞凋亡，并激活MAPKs、p53信号通路，但其抗癌机制尚需深入研究。为此，本课题组通过体外和体内实验研究M抗肺癌作用；研究M抗肺癌的作用机制及在体外和体内对调控细胞存活和凋亡的关键因子的影响；利用抑制剂和siRNA分别抑制肺癌细胞内MAPKs的活性，证实M诱导肺癌细胞凋亡作用是否依赖MAPKs；分别采用p53突变型/缺失型/野生型的肺癌细胞，研究M诱导的细胞凋亡作用是否依赖p53，并采用siRNA抑制p53野生型肺癌细胞内p53表达，进一步证实M是否通过p53诱导肺癌细胞凋亡。研究结果不仅有助于揭示M抗肺癌作用及机制，并为M成为肺癌潜在的化疗治疗药物提供理论基础和实验依据。

The incidence and mortality of lung cancer rank top of different types of tumors in china. The anticancer activity of C18H17NO6 (M) is better than that of cisplatin and paclitaxel. M inhibits lung cancer cells and has good drug safety and stability in vivo. We have found that M can selectively inhibit the proliferation of lung cancer cells, induce G2/M phase arrest, promote cell apoptosis, and activate MAPK and p53 signaling pathways, but its anti-cancer mechanism needs further study. Therefore, firstly we are going to invesitigate the anticancer effects of M, and explore whether this drug affects the expression of key proteins which reglute cell proliferation and apoptosis. Secondly, by using specific inhibitors and siRNA to block the activity of MAPKs, we will explore whether M-induced anticancer activities depends on MAPKs. Thirdly, by using p53 WT/null/mutation lung cancer cells, we are going to confirm the role of p53 in M-induced anticancer effects, and siRNA was used to silence p53 in p53 WT lung cancer cells to further confirm M-induced anticancer effects was p53-dependent. The results not only help to reveal the anti-lung cancer effect and mechanism of M, but also provide theoretical and experimental basis for M to become a potential chemotherapeutic drug for lung cancer.