Metabolic Signalling Group, Curtin Medical School, Curtin Health Innovation Research Institute, Curtin University, Perth 6102, Australia.
Backreef Oil Pty Ltd., Perth 6015, Australia.
Int J Mol Sci. 2024 Feb 16;25(4):2340. doi: 10.3390/ijms25042340.
Among diverse cancers, pancreatic cancer is one of the most aggressive types due to inadequate diagnostic options and treatments available. Therefore, there is a necessity to use combination chemotherapy options to overcome the chemoresistance of pancreatic cancer cells. Plumbagin and xanthohumol, natural compounds isolated from the Plumbaginaceae family and respectively, have been used to treat various cancers. In this study, we investigated the anticancer effects of a combination of plumbagin and xanthohumol on pancreatic cancer models, as well as the underlying mechanism. We have screened in vitro numerous plant-derived extracts and compounds and tested in vivo the most effective combination, plumbagin and xanthohumol, using a transgenic model of pancreatic cancer KPC (KrasLSL.G12D/+; p53R172H/+; PdxCretg/+). A significant synergistic anticancer activity of plumbagin and xanthohumol combinations on different pancreatic cancer cell lines was found. The combination treatment of plumbagin and xanthohumol influences the levels of B-cell lymphoma (BCL2), which are known to be associated with apoptosis in both cell lysates and tissues. More importantly, the survival of a transgenic mouse model of pancreatic cancer KPC treated with a combination of plumbagin and xanthohumol was significantly increased, and the effect on BCL2 levels has been confirmed. These results provide a foundation for a potential new treatment for pancreatic cancer based on plumbagin and xanthohumol combinations.
在各种癌症中，胰腺癌由于诊断选择和治疗方法有限，是最具侵袭性的癌症之一。因此，有必要使用联合化疗方案来克服胰腺癌细胞的耐药性。来源于 Plumbaginaceae 科的天然化合物白花丹醌和黄腐醇已被用于治疗各种癌症。在这项研究中，我们研究了白花丹醌和黄腐醇联合治疗胰腺癌模型的抗癌作用及其潜在机制。我们在体外筛选了许多植物提取物和化合物，并在体内使用胰腺癌 KPC（KrasLSL.G12D/+; p53R172H/+; PdxCretg/+）转基因模型测试了最有效的联合治疗药物，即白花丹醌和黄腐醇。我们发现，白花丹醌和黄腐醇联合使用对不同的胰腺癌细胞系具有显著的协同抗癌活性。白花丹醌和黄腐醇联合治疗会影响 B 细胞淋巴瘤（BCL2）的水平，BCL2 与细胞裂解物和组织中的细胞凋亡有关。更重要的是，用白花丹醌和黄腐醇联合治疗的胰腺癌 KPC 转基因小鼠模型的存活率显著提高，BCL2 水平的变化得到了证实。这些结果为基于白花丹醌和黄腐醇联合治疗的胰腺癌潜在新治疗方法提供了依据。
