Study uncovers molecular mechanism of Lobelia chinensis Lour in suppressing liver cancer
Multiomics analysis identifies key compounds and protein targets offering new avenues for liver cancer therapy
image: LCL-liver cancer core targets identification. (A) Starting with the compounds from LCL, a series of screening analyses were conducted, integrating liver cancer-related data to identify intersecting targets. A PPI analysis was then performed to determine the key targets. (B) Univariate Cox regression analysis identified 5 prognostic genes (p < 0.05). (C) Cross-validation curve of LASSO regression. The dotted line on the left marks the λ value corresponding to the best model fit. (D) Coefficient path diagram of 4 genes, with different-colored lines representing the coefficient changes for each gene. (E) Multivariate Cox regression analysis identified 3 core genes related to prognosis. (F) In the training cohort, KM survival analyses were performed for the high-risk and low-risk groups. The low-risk and high-risk groups were delineated by dotted lines. (G) In the testing cohort, the survival analysis and associated displays were repeated, with the dotted line again used to define the high-risk and low-risk groups.
Credit: Zixuan Yang, Li Song, Hongru Chen, Yaoyao Chen, Youyi Xie, Jumin Xie
Liver cancer is a deleterious disease that accounts for a significant portion of cancer-related deaths worldwide. despite advancements in medical technology, the morbidity and mortality rates remain high, creating an urgent need for safe and effective therapeutic agents. A recent study published in the journal Med Research explores the potential of Lobelia chinensis Lour (LCL), a plant with a long history of medicinal use, in treating hepatocellular carcinoma.
LCL is well-known in traditional medicine for its heat-clearing, detoxifying, and diuretic properties. While previous studies have suggested its antitumor activity, the specific molecular mechanisms and active ingredients responsible for these effects have remained unclear. To address this, the research team employed a comprehensive multiomics approach, integrating network pharmacology, bioinformatics, and molecular dynamics simulations.
The researchers screened public databases and identified 33 active molecules within LCL, corresponding to nearly 600 potential protein targets. By intersecting these targets with gene expression data from liver cancer tissues, the team isolated 56 common targets. Further analysis using a protein-protein interaction network narrowed this down to three core targets crucial for cancer cell survival: CCNB1, CCNB2, and CDK1.
The study revealed that these three genes are significantly overexpressed in liver cancer tissues compared to normal tissues and are closely correlated with poor patient prognosis and higher mortality rates. CDK1, a cell cycle protein kinase, works in complex with cyclins (CCNB1 and CCNB2) to drive cell division. The upregulation of these proteins accelerates the malignant transformation and proliferation of cancer cells.
Through molecular docking and dynamics simulations, the researchers demonstrated that specific bioactive components of LCL—namely Asiatic Acid, Lobelanine, and Lobeline—exhibit strong binding affinity to these core targets. By binding to CCNB1, CCNB2, and CDK1, these compounds may effectively disrupt the cell cycle of liver cancer cells, thereby exerting an anticancer effect.
The authors note that while these genes serve as potential diagnostic markers, they also represent promising therapeutic targets. This study provides a scientific basis for the use of LCL in oncology and offers a theoretical framework for developing new strategies for the early diagnosis and treatment of liver cancer.