ChanLingGao alleviates intestinal mucosal barrier damage and suppresses the onset and progression of Colorectal cancer in AOM/DSS murine model.

BACKGROUND: The occurrence of Colorectal Cancer (CRC) is influenced by various factors, including host susceptibility, immune imbalance, and environmental triggers. Numerous studies have underscored the critical role of chronic intestinal inflammation and dysbiosis in the development of CRC. Traditional Chinese Medicine (TCM) holds unique advantages in regulating the intricate process of and comprehensive treatment for systemic disease. Previous investigations by our team have confirmed the anti-cancer properties of the TCM compound ChanLingGao (CLG), including inhibiting cancer cell migration, and alleviating bone cancer pain. However, the mechanisms underlying its efficacy in alleviating chronic intestinal inflammation, modulating the gut microbiota, and protecting the intestinal mucosal barrier remain largely unknown. PURPOSE: This study aims to explore the inhibitory effects of CLG on CRC tumors in mice and its potential mechanisms. METHODS: A chronic inflammation-related CRC mouse model was established using AOM/DSS. The study examined the mechanisms of intestinal inflammation and tumor cell proliferation through intestinal histological morphology. High-throughput sequencing was employed to analyze changes in gut microbiota diversity and intestinal mucosal barrier integrity in CRC mice. Based on network pharmacology target prediction and Wnt/ß-catenin signaling pathway analysis, the study analyzed and discussed the potential mechanisms of CLG on CRC. RESULTS: CLG significantly ameliorated weight loss and increased survival rates in CRC mice, while suppressing tumor growth in the intestinal tract. Post-CLG treatment improved intestinal inflammation in CRC mice, with a significant reduction in inflammatory factors IL-6, IL-23 and LCN2, and inhibition of tumor cell proliferation markers Proliferating Cell Nuclear Antigen (PCNA), Recombinant Ki-67 Protein (Ki-67), and CCND1. 16sV3-V4 region microbiota sequencing results indicated that CLG improved dysbiosis, and significantly increased the abundance of Akkermansia bacteria, further promoting the expression of MUC-2 protein and mucin secretion. Additionally, CLG prevented the disruption of intestinal epithelial cell junction proteins Occludin, Claudin-1, ZO-1, and E-cadherin, restored the number of goblet cells, and preserved the integrity of the intestinal mucosal barrier. Further experiments suggested that CLG inhibited abnormal activation of the Wnt/ß-catenin pathway, and its potential mechanism in maintaining mucosal barrier integrity might be related to blocking Wnt/ß-catenin pathway. CONCLUSIONS: This study demonstrates that CLG can inhibit CRC tumor growth by regulating the gut microbiota structure, reducing intestinal inflammation, improving intestinal mucosal barrier function, and inhibiting the complex process of cancer cell proliferation. This provides new clinical insights into the "membrane-oriented" treatment of CRC with CLG.

Chanling Gao suppresses colorectal cancer via PI3K/Akt/mTOR pathway modulation and enhances quality of survival.

The Chinese medicine formula Chanling Gao (CLG) exhibits significant tumor inhibitory effects in colorectal cancer (CRC) nude mice. However, the detailed mechanisms remain elusive. CRC in situ nude mouse models were treated with CLG. Small animal magnetic resonance imaging (MRI) tracked tumor progression, and overall health metrics such as food and water intake, body weight, and survival were monitored. Posttreatment, tissues and blood were analyzed for indicators of tumor inhibition and systemic effects. Changes in vital organs were observed via stereoscope and hematoxylin-eosin staining. Immunohistochemistry quantified HIF-1α and P70S6K1 protein expression in xenografts. Double labeling was used to statistically analyze vascular endothelial growth factor (VEGF) and CD31 neovascularization. Enzyme-linked immunosorbent assay was used to determine the levels of VEGF, MMP-2, MMP-9, IL-6, and IL-10 in serum, tumors, and liver. Western blotting was used to assess the expression of the PI3K/Akt/mTOR signaling pathway-related factors TGF-ß1 and smad4 in liver tissues. CLG inhibited tumor growth, improved overall health metrics, and ameliorated abnormal blood cell counts in CRC nude mice. CLG significantly reduced tumor neovascularization and VEGF expression in tumors and blood. It also suppressed HIF-1α, EGFR, p-PI3K, Akt, p-Akt, and p-mTOR expression in tumors while enhancing PTEN oncogene expression. Systemic improvements were noted, with CLG limiting liver metastasis, reducing pro-inflammatory cytokines IL-6 and IL-10 in liver tissues, decreasing MMP-2 in blood and MMP-2 and MMP-9 in tumors, and inhibiting TGF-ß1 expression in liver tissues. CLG can enhance survival quality and inhibit tumor growth in CRC nude mice, likely through the regulation of the PI3K/Akt/mTOR signaling pathway.

Oncological outcomes of laparoscopic versus open surgery in pT4 colon cancers: A systematic review and meta-analysis.

BACKGROUND: Widespread adoption of minimally invasive surgery for colon cancer has achieved improved short-term benefits and better long-term oncological outcomes compared with open surgery. However, it is still controversial whether laparoscopic surgery is suitable for patients with stage T4 colon cancer. The aim of this meta-analysis was to compare short- and long-term oncological outcomes associated with laparoscopic and conventional open surgery for pT4 colon cancer. METHODS: Published studies from 2003 to 2018 comparing oncological outcomes following laparoscopic and open surgery for pT4 colon cancer were systematically searched. Data on conversion rate, R0 resection rate, number of harvested lymph nodes, morbidity and mortality, and overall survival (OS) and disease-free survival (DFS) were subjected to meta-analysis using fixed-effect and random-effect models. RESULTS: Twelve observational studies met the inclusion criteria with a total of 2396 cases (1250 laparoscopic and 1146 open). There was no significant difference in R0 resection rate [relative risk (RR) = 1.007; 95% confidence interval (CI) = 0.935-1.085; P = 0.850], number of harvested lymph nodes (MD = 0.004; 95% CI = -0.139 to 0.148; P = 0.951), mortality (RR = 0.509; 95% CI = 0.176-1.470; P = 0.212), and 3-year OS (RR = 1.056; 95% CI = 0.939-1.188; P = 0.360), 5-year OS (RR = 1.003; 95% CI = 0.883-1.139; P = 0.966), 3-year DFS (RR = 1.032; 95% CI = 0.903-1.179; P = 0.642), and 5-year DFS (RR = 0.995; 95% CI = 0.868-1.140; P = 0.973) between the groups. The rate of conversion from laparoscopic to open procedures was 10.7% (95% CI = 0.090-0.124). There was a significant difference in incidence of complications within 30 postoperative days between laparoscopic and open surgery (RR = 0.703; 95% CI = 0.564-0.876; P = 0.002). CONCLUSION: Laparoscopic surgery is safe and feasible in pT4 colon cancer, oncological outcomes are similar, and more importantly, there are fewer postoperative complications compared with open surgery.