Purple flowered Houttuynia cordata glycoside exerts anti liver cancer effects by regulating the CXCL5-ERK/MEK signaling axis
Liver cancer has become a common digestive system tumor disease in clinical practice, with complex pathogenic factors and mechanisms leading to a high mortality rate. Currently, surgical resection is the main treatment method in clinical practice, but the postoperative survival of many patients is very poor, mainly due to the high metastasis of liver cancer leading to tumor recurrence. The combination of surgery and effective postoperative medication is of great significance in improving the survival of liver cancer patients. Currently, clinical drugs for treating liver cancer include fluorouracil, but they have certain toxic side effects. Traditional Chinese medicine has a certain auxiliary therapeutic effect and minimal side effects in the treatment of liver cancer. Studies have shown that “Yiqi Huoxue Tang” can effectively prolong the postoperative survival of liver cancer patients. Based on years of experience in treating liver cancer with traditional Chinese medicine, our department has modified and improved the decoction of “Yiqi Huoxue Tang” by adding Qianghuo. The main active substance of Qianghuo is rutin, which has been proven to have inhibitory effects on cervical cancer cells. Its mechanism may be related to autophagy related cell apoptosis, but there is no research report on the effect of rutin on liver cancer. Therefore, this study mainly explores the role of rutin on liver cancer and its possible targets and signaling pathways.

 

 

Liver cancer has become a common malignant tumor disease in clinical practice, with a complex pathogenesis and limited treatment drugs. Currently, the treatment method for patients with advanced liver cancer is surgical resection. However, the high metastatic nature of liver cancer leads to its high metastasis and recurrence rate in the body, resulting in poor postoperative prognosis for patients. Scholars have proposed that postoperative combination of certain drug treatments can effectively prolong the survival of liver cancer patients. Traditional Chinese medicine has received increasing attention from Chinese medicine researchers in recent years, especially in the study of the effects of monomeric active substances extracted from traditional Chinese medicine on tumors. In this study, purple clover glycoside was extracted from the traditional Chinese medicine Qianghuo as a monomeric drug. Currently, there is limited research on the anti-tumor effects of purple clover glycoside, and only a few literature reports that it can effectively inhibit the proliferation of cervical cancer cells. After surgery, all hospitalized liver cancer patients in our department received certain prognostic treatment with the “Modified Yiqi Huoxue Decoction”. This decoction contains the traditional Chinese medicine Qianghuo. Therefore, this study proposes a hypothesis: whether the effective substance in Qianghuo, purple pre Hu glycoside, can exert anti-cancer effects on liver cancer, and what the specific regulatory mechanism is, will be the focus of this study.

This study first observed the effects of different concentrations of resveratrol on liver cancer cells, and found that 20ng/mL of resveratrol had the strongest inhibitory effect on liver cancer cells HepG2 and MHCC-97H, indicating that resveratrol can inhibit the proliferation of liver cancer cells HepG2 and MHCC-97H. At the same time, clone formation experiments further confirmed this, laying a foundation for further research. The migration and invasion ability are the basis and key factors for the metastasis of liver cancer in vivo. Therefore, the effect of resveratrol on the migration and invasion ability of liver cancer cells was observed. The results showed that resveratrol effectively inhibited the migration and invasion ability of HepG2 and MHCC-97H cells, indicating that resveratrol can exert anticancer effects on liver cancer. In order to further explain and elucidate the mechanism of the anticancer effect of paeoniflorin, differential gene analysis was conducted through RNA seq. It was found that after treatment with paeoniflorin in HepG2 cells, after screening, genes such as CXCL5, ALYREF, SRPK2, IGF-1, and RYR2 were found to be downregulated in the forefront, while genes such as ING1, PTEN, BRCA1, NF-1, and APC were upregulated in the forefront, with CXCL5 showing the highest downregulation fold. CXCL5 is an epithelial derived neutrophil chemokine that activates the ERK/MEK signaling pathway by binding to its specific receptor CXCR2, promoting angiogenesis and mediating tumor growth, infiltration, and metastasis. Previous studies have shown that the expression of CXCL5 is significantly increased in tumor tissues such as liver cancer, gastric cancer, prostate cancer, and non-small cell lung cancer. Therefore, this study will focus on the effect of resveratrol on CXCL5 in liver cancer cells. The results showed that resveratrol treatment significantly inhibited the expression of CXCL5 in HepG2 and MHCC-97H cells, suggesting that the possible target molecule of resveratrol is CXCL5.

CXCL5 is a chemotactic factor derived from neutrophils, which is closely related to tumor immune regulation signals. Studies have shown that the downstream regulatory pathway of CXCL5 is the ERK/MEK tumor immune signaling pathway, which plays a pro cancer role in the occurrence and development of various tumors. In order to further elucidate the anticancer mechanism of resveratrol on liver cancer, changes in the ERK/MEK tumor immune signaling pathway in HepG2 and MHCC-97H cells treated with resveratrol were observed. The results showed that resveratrol can significantly inhibit the phosphorylation of ERK and MEK, thereby inhibiting the activation of the ERK/MEK signaling pathway. When si RNA is silenced, CXCL5 in HepG2 and MHCC-97H cells was inhibited. After expression, the phosphorylation inhibition of ERK and MEK by anthocyanins almost disappeared, indicating that anthocyanins may exert anticancer effects by regulating the ERK/MEK signaling pathway through CXCL5.

The above research results suggest that resveratrol has an anticancer effect on liver cancer, and its possible target molecule is CXCL5. At the same time, resveratrol can inhibit the activation of the tumor immune signaling pathway ERK/MEK in liver cancer cells. These studies provide a certain research basis and theoretical basis for the anticancer effect of resveratrol on liver cancer. Although this study suggests that anthocyanins can exert anti-cancer effects, the research is mainly conducted in vitro. Next, we will further investigate the effects of anthocyanins on liver cancer in vivo, and focus on how anthocyanins regulate CXCL5, with a particular emphasis on their specific regulatory mechanisms in tumor immunity.