A Network Pharmacology-based Mechanism of the Traditional Chinese Medicine Formula Li Kun Zhi Ji acting on Colon Cancer

Abstract

Backgrounds: Li Kun Zhi Ji (LKZJ) is a traditional Chinese medicine formula that effectively improves the immune system. However, the mechanism of its action against cancer remains unknown. Our study aimed to determine whether LKZJ inhibits the growth of the human colon cancer cell line HCT-116, and we performed in vitro experiments to further explore the associated molecular mechanisms. Objective: We explored the antitumor function and the mechanism of LKZJ against human colon cancer cells. Methods: We selected the effective components of LKZJ. Then, the potential targets of these components were obtained against colon cancer, and an “LKZJ-targets-colon cancer” network was constructed. After that, a CCK-8 assay was used to assess cell viability. Next, apoptosis was analyzed with PI/Annexin V assay using flow cytometry. Finally, western blotting was carried out to determine the expression levels of the protein. Results: We obtained 36 effective LKZJ components and identified 225 candidate targets acting on colon cancer. We demonstrated that the cell viability of HCT-116 cells had significantly decreased after treatment of LKZJ. The suppression of HCT-116 proliferation by LKZJ through inducing apoptosis was determined using Flow cytometry. In addition, mitochondria-associated apoptosis was stimulated, and the down-regulation of Bcl-2 and up-regulation of Bax and Bad were observed. LKZJ also attenuated the PI3K/Akt signaling pathway through western blotting. Conclusion: Our study revealed that LKZJ induced HCT-116 cell line apoptosis through the PI3K/Akt apoptotic pathway. Our results indicated that LKZJ could be a possible therapeutic agent against human colon cancer.