Xu Dongchao, Shen Hongzhang, Tian Mengyao, Chen Wangyang, Zhang Xiaofeng
Department of Gastroenterology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou310000, China.
Hangzhou Institute of Digestive Diseases, Hangzhou310000, China.
J Cancer. 2022 Mar 28;13(7):2050-2060. doi: 10.7150/jca.65875. eCollection 2022.
Pancreatic cancer is one of the most aggressive solid malignancies, as it has a 5-year survival rate of less than 10%. The growth and invasion of pancreatic cancer cells into normal tissues and organs make resection and treatment difficult. Finding an effective chemotherapy drug for this disease is crucial. In this study, we selected the tetracyclic triterpenoid compound cucurbitacin I, which may be used as a potential therapeutic drug for treating pancreatic cancer. First, we found that cucurbitacin I inhibited pancreatic cancer proliferation in a dose-time dependent manner. Further studies have shown that cucurbitacin I blocks the cell cycle of pancreatic cancer in the G2/M phase and induces cell apoptosis. In addition, under the action of the compound, the invasion ability of cells was greatly reduced and markedly impaired the growth of pancreatic tumour xenografts in nude mice. Furthermore, the decrease in pancreatic cancer cell proliferation caused by cucurbitacin I appeared to involve JAK2/STAT3 signalling pathway inhibition, and the use of JAK2/STAT3 activators effectively restored the inhibition. In conclusion, our research may provide a basis for the further development of pancreatic cancer treatment drugs.
胰腺癌是最具侵袭性的实体恶性肿瘤之一，其5年生存率低于10%。胰腺癌细胞向正常组织和器官的生长与侵袭使得切除和治疗变得困难。找到针对这种疾病的有效化疗药物至关重要。在本研究中，我们选择了四环三萜类化合物葫芦素I，它可能用作治疗胰腺癌的潜在治疗药物。首先，我们发现葫芦素I以剂量-时间依赖性方式抑制胰腺癌增殖。进一步研究表明，葫芦素I在G2/M期阻断胰腺癌的细胞周期并诱导细胞凋亡。此外，在该化合物作用下，细胞的侵袭能力大大降低，并显著抑制裸鼠体内胰腺肿瘤异种移植的生长。此外，葫芦素I引起的胰腺癌细胞增殖减少似乎涉及JAK2/STAT3信号通路抑制，并且使用JAK2/STAT3激活剂可有效恢复这种抑制作用。总之，我们的研究可能为胰腺癌治疗药物的进一步开发提供依据。
